99 results on '"Tuuri T"'
Search Results
2. P-659 Natural cycle versus medically programmed cycle in frozen embryo transfer: a retrospective analysis
- Author
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Sneck, M, primary, Hyden-Granskog, C, additional, Granroth-Wilding, H, additional, Savolainen-Peltonen, H, additional, Tuuri, T, additional, Tapanainen, J S, additional, and Luiro, K, additional
- Published
- 2023
- Full Text
- View/download PDF
3. P-422 Ovarian tissue vitrification as a low-technology and cost-effective protocol for female fertility preservation: a bovine study
- Author
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Deligiannis, S P, primary, Kask, K, additional, Modhukur, V, additional, Ivask, M, additional, Jaakma, Ü, additional, Damdimopoulou, P, additional, Tuuri, T, additional, Velthut-Meikas, A, additional, and Salumets, A, additional
- Published
- 2023
- Full Text
- View/download PDF
4. P-793 The effect of Nuclear Receptor Subfamily 5 Group A Member 1 (NR5A1) in human ovarian somatic cell development
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Danti, L, primary, Lundin, K, additional, Sepponen, K, additional, Yohannes, D.A, additional, Kere, J, additional, Tuuri, T, additional, and Tapanainen, J, additional
- Published
- 2022
- Full Text
- View/download PDF
5. Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells
- Author
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Sepponen, K. (Kirsi), Lundin, K. (Karolina), Yohannes, D. A. (Dawit A.), Vuoristo, S. (Sanna), Balboa, D. (Diego), Poutanen, M. (Matti), Ohlsson, C. (Claes), Hustad, S. (Steinar), Bifulco, E. (Ersilia), Paloviita, P. (Pauliina), Otonkoski, T. (Timo), Ritvos, O. (Olli), Sainio, K. (Kirsi), Tapanainen, J. S. (Juha S.), Tuuri, T. (Timo), Sepponen, K. (Kirsi), Lundin, K. (Karolina), Yohannes, D. A. (Dawit A.), Vuoristo, S. (Sanna), Balboa, D. (Diego), Poutanen, M. (Matti), Ohlsson, C. (Claes), Hustad, S. (Steinar), Bifulco, E. (Ersilia), Paloviita, P. (Pauliina), Otonkoski, T. (Timo), Ritvos, O. (Olli), Sainio, K. (Kirsi), Tapanainen, J. S. (Juha S.), and Tuuri, T. (Timo)
- Abstract
Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1 during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1 expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without NR5A1 activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of NR5A1 expression. Of those, we identified novel gonad-related putative NR5A1 targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, NR5A1 activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of NR5A1 we have for the first time, been able to examine in detail the effects of NR5A1 in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans.
- Published
- 2022
6. Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors:modeling the function of an inactivating receptor mutation
- Author
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Lundin, K. (K.), Sepponen, K. (K.), Väyrynen, P. (P.), Liu, X. (X.), Yohannes, D. A. (D. A.), Survila, M. (M.), Ghimire, B. (B.), Känsäkoski, J. (J.), Katayama, S. (S.), Partanen, J. (J.), Vuoristo, S. (S.), Paloviita, P. (P.), Rahman, N. (N.), Raivio, T. (T.), Luiro, K. (K.), Huhtaniemi, I. (I.), Varjosalo, M. (M.), Tuuri, T. (T.), Tapanainen, J. S. (J. S.), Lundin, K. (K.), Sepponen, K. (K.), Väyrynen, P. (P.), Liu, X. (X.), Yohannes, D. A. (D. A.), Survila, M. (M.), Ghimire, B. (B.), Känsäkoski, J. (J.), Katayama, S. (S.), Partanen, J. (J.), Vuoristo, S. (S.), Paloviita, P. (P.), Rahman, N. (N.), Raivio, T. (T.), Luiro, K. (K.), Huhtaniemi, I. (I.), Varjosalo, M. (M.), Tuuri, T. (T.), and Tapanainen, J. S. (J. S.)
- Abstract
Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein–protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.
- Published
- 2022
7. Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation
- Author
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Lundin, K, primary, Sepponen, K, additional, Väyrynen, P, additional, Liu, X, additional, Yohannes, D A, additional, Survila, M, additional, Ghimire, B, additional, Känsäkoski, J, additional, Katayama, S, additional, Partanen, J, additional, Vuoristo, S, additional, Paloviita, P, additional, Rahman, N, additional, Raivio, T, additional, Luiro, K, additional, Huhtaniemi, I, additional, Varjosalo, M, additional, Tuuri, T, additional, and Tapanainen, J S, additional
- Published
- 2022
- Full Text
- View/download PDF
8. P–699 Multi-scale study of the architecture, topography and mechanics of the human ovary from prepuberty to menopause: a blueprint for next-generation bioengineering and diagnosis
- Author
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Ouni, E, primary, Haas, K T, additional, Peaucelle, A, additional, Va. Kerk1, O, additional, Dolmans, M M, additional, Tuuri, T, additional, Otala, M, additional, and Andrad. Amorim, C, additional
- Published
- 2021
- Full Text
- View/download PDF
9. Small RNA expression and miRNA modification dynamics in human oocytes and early embryos
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Paloviita, P. (Pauliina), Hydén-Granskog, C. (Christel), Yohannes, D. A. (Dawit A.), Paluoja, P. (Priit), Kere, J. (Juha), Tapanainen, J. S. (Juha S.), Krjutškov, K. (Kaarel), Tuuri, T. (Timo), Võsa, U. (Urmo), and Vuoristo, S. (Sanna)
- Abstract
Small noncoding RNAs (sRNAs) play important roles during the oocyte-to-embryo transition (OET), when the maternal phenotype is reprogrammed and the embryo genome is gradually activated. The transcriptional program driving early human development has been studied with the focus mainly on protein-coding RNAs, and expression dynamics of sRNAs remain largely unexplored. We profiled sRNAs in human oocytes and early embryos using an RNA-sequencing (RNA-seq) method suitable for low inputs of material. We show that OET in humans is temporally coupled with the transition from predominant expression of oocyte short piRNAs (os-piRNAs) in oocytes, to activation of microRNA (miRNA) expression in cleavage stage embryos. Additionally, 3′ mono- and oligoadenylation of miRNAs is markedly increased in zygotes. We hypothesize that this may modulate the function or stability of maternal miRNAs, some of which are retained throughout the first cell divisions in embryos. This study is the first of its kind elucidating the dynamics of sRNA expression and miRNA modification along a continuous trajectory of early human development and provides a valuable data set for in-depth interpretative analyses.
- Published
- 2021
10. Does long in vitro culture promote large for gestational age babies?
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Mäkinen, S., Söderström-Anttila, V., Vainio, J., Suikkari, A.-M., and Tuuri, T.
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- 2013
- Full Text
- View/download PDF
11. Does long in vitro culture promote large for gestational age babies?: O-180
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Tuuri, T., Mäkinen, S., Söderström-Anttila, V., Vainio, J., and Suikkari, A. M.
- Published
- 2012
12. Complement in human pre-implantation embryos:attack and defense
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Reichhardt, M. P. (Martin P.), Lundin, K. (Karolina), Lokki, A. I. (A. Inkeri), Recher, G. (Gaëlle), Vuoristo, S. (Sanna), Katayama, S. (Shintaro), Tapanainen, J. S. (Juha S.), Kere, J. (Juha), Meri, S. (Seppo), and Tuuri, T. (Timo)
- Subjects
pre-implantation ,mucosal immunology ,reproductive immunology ,embryo ,complement ,development - Abstract
It is essential for early human life that mucosal immunological responses to developing embryos are tightly regulated. An imbalance of the complement system is a common feature of pregnancy complications. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus, far, immunological imbalance has been considered in stages of pregnancy following implantation. We here show that complement activation against developing human embryos takes place already at the pre-implantation stage. Using confocal microscopy, we observed deposition of activation products on healthy developing embryos, which highlights the need for strict complement regulation. We show that embryos express complement membrane inhibitors and bind soluble regulators. These findings show that mucosal complement targets human embryos, and indicate potential adverse pregnancy outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing revealed cellular expression of complement activators. This shows that the embryonic cells themselves have the capacity to express and activate C3 and C5. The specific local embryonic expression of complement components, regulators, and deposition of activation products on the surface of embryos suggests that complement has immunoregulatory functions and furthermore may impact cellular homeostasis and differentiation at the earliest stages of life.
- Published
- 2019
13. Association between sequence variations in genes encoding human zona pellucida glycoproteins and fertilization failure in IVF
- Author
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Männikkö, M., Törmälä, R.-M., Tuuri, T., Haltia, A., Martikainen, H., Ala-Kokko, L., Tapanainen, J.S., and Lakkakorpi, J.T.
- Published
- 2005
14. rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology
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Marjonen, H., Auvinen, P., Kahila, H., Tšuiko, O., Kõks, S., Tiirats, A., Viltrop, T., Tuuri, T., Söderström-Anttila, V., Suikkari, A-M, Salumets, A., Tiitinen, A., Kaminen-Ahola, N., Marjonen, H., Auvinen, P., Kahila, H., Tšuiko, O., Kõks, S., Tiirats, A., Viltrop, T., Tuuri, T., Söderström-Anttila, V., Suikkari, A-M, Salumets, A., Tiitinen, A., and Kaminen-Ahola, N.
- Abstract
Background Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 (IGF2)/H19 locus known to be important for normal growth. This locus is regulated by H19 imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF, associates with a genotype-specific trend to the DNA methylation. Due to this association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18 ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously conceived pregnancies as controls were recruited in Finland and Estonia for genotype-specific examination. DNA methylation levels at the H19 ICR, H19 DMR, and long interspersed nuclear elements in placental tissue were explored by MassARRAY EpiTYPER (n = 122). Allele-specific changes in the methylation level of H19 ICR in placental tissue (n = 26) and white blood cells (WBC, n = 8) were examined by bisulfite sequencing. Newborns’ (n = 243) anthropometrics was analyzed by using international growth standards. Results A consistent trend of genotype-specific decreased methylation level was observed in paternal allele of rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A genotype, at H19 ICR in ART placentas. This hypomethylation was not detected in WBCs. Also genotype-specific differences in FRESH-derived newborns’ birth weight and head circumference were observed (P = 0.04, P = 0.004, respectively): FRESH-derived newborns with G/G genotype were heavier (P = 0.04) and had larger head circumference (P = 0.002) compared to newborns with A/A genotype. Also, the placental weight and birth weight of controls, FRESH- and FET-derived newborns differed significantly in r
- Published
- 2018
15. Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage
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Amps, K., Andrews, P.W., Anyfantis, G., Armstrong, L., Avery, S., Baharvand, H., Baker, J., Baker, D., Munoz, M.B., Beil, S., Benvenisty, N., Ben-Yosef, D., Biancotti, J.C., Bosman, A., Brena, R.M., Brison, D., Caisander, G., Camarasa, M.V., Chen, J.M., Chiao, E., Choi, Y.M., Choo, A.B.H., Collins, D., Colman, A., Crook, J.M., Daley, G.Q., Dalton, A., Sousa, P.A. de, Denning, C., Downie, J., Dvorak, P., Montgomery, K.D., Feki, A., Ford, A., Fox, V., Fraga, A.M., Frumkin, T., Ge, L., Gokhale, P.J., Golan-Lev, T., Gourabi, H., Gropp, M., Lu, G.X., Hampl, A., Harron, K., Healy, L., Herath, W., Holm, F., Hovatta, O., Hyllner, J., Inamdar, M.S., Irwanto, A.K., Ishii, T., Jaconi, M., Jin, Y., Kimber, S., Kiselev, S., Knowles, B.B., Kopper, O., Kukharenko, V., Kuliev, A., Lagarkova, M.A., Laird, P.W., Lako, M., Laslett, A.L., Lavon, N., Lee, D.R., Lee, J.E., Li, C.L., Lim, L.S., Ludwig, T.E., Ma, Y., Maltby, E., Mateizel, I., Mayshar, Y., Mileikovsky, M., Minger, S.L., Miyazaki, T., Moon, S.Y., Moore, H., Mummery, C., Nagy, A., Nakatsuji, N., Narwani, K., Oh, S.K.W., Oh, S.K., Olson, C., Otonkoski, T., Pan, F., Park, I.H., Pells, S., Pera, M.F., Pereira, L.V., Qi, O., Raj, G.S., Reubinoff, B., Robins, A., Robson, P., Rossant, J., Salekdeh, G.H., Schulz, T.C., Sermon, K., Mohamed, J.S., Shen, H., Sherrer, E., Sidhu, K., Sivarajah, S., Skottman, H., Spits, C., Stacey, G.N., Strehl, R., Strelchenko, N., Suemori, H., Sun, B.W., Suuronen, R., Takahashi, K., Tuuri, T., Venu, P., Verlinsky, Y., Ward-van Oostwaard, D., Weisenberger, D.J., Wu, Y., Yamanaka, S., Young, L., Zhou, Q., Int Stem Cell Initiative, Bosman, Alexis, Feki, Anis, and Jaconi, Marisa
- Subjects
Inhibitor of Differentiation Protein 1 ,Cellular differentiation ,Ethnic Groups/genetics ,Chromosomes, Human, Pair 20 ,Inhibitor of Differentiation Protein 1/genetics/metabolism ,Growth ,ddc:616.07 ,Applied Microbiology and Biotechnology ,0302 clinical medicine ,Induced Pluripotent Stem Cells/cytology ,Ethnicity ,Growth/genetics ,Induced pluripotent stem cell ,Genetics ,CÉLULAS-TRONCO ,0303 health sciences ,Gene Expression Regulation, Developmental ,RNA-Binding Proteins ,Cell Differentiation ,Amplicon ,Molecular Medicine ,Stem cell ,Biotechnology ,Homeobox protein NANOG ,Genotype ,Cell Differentiation/genetics ,Induced Pluripotent Stem Cells ,bcl-X Protein ,Biomedical Engineering ,Bioengineering ,Biology ,Polymorphism, Single Nucleotide ,Selection, Genetic/genetics ,Cell Line ,Clonal Evolution ,03 medical and health sciences ,Bcl-X Protein/genetics/metabolism ,Humans ,RNA-Binding Proteins/genetics/metabolism ,Selection, Genetic ,Embryonic Stem Cells ,030304 developmental biology ,Embryonic Stem Cells/cytology ,Genetic Variation ,DNA Methylation ,Molecular biology ,Embryonic stem cell ,Chromosomes, Human, Pair 20/genetics ,Clonal Evolution/genetics ,Cell culture ,Chromosome 20 ,030217 neurology & neurosurgery - Abstract
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.
- Published
- 2011
16. 'Kun maalaa, on mukava samalla kuunnella, mitä vois maalata':kuudesluokkalaisten kokemuksia musiikkimaalauksesta
- Author
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Tuuri, T. (Tiina)
- Subjects
Education - Abstract
Pro gradu -tutkielmani tarkoituksena on selvittää kuudesluokkalaisten käsityksiä ja kokemuksia musiikkimaalauksesta työskentelytapana ja oppimismenetelmänä musiikkimaalausprosessin eri vaiheissa. Musiikkimaalaukseen liittyvää tutkimusta on tehty melko vähän, ja aiempi tutkimus keskittyy enemmänkin tuotosten tulkintaan ja musiikkimaalauksen musiikkiterapeuttisiin lähtökohtiin. Tutkimukseni pyrkimyksenä onkin nyt laajentaa musiikkimaalaukseen liittyvää tutkimuskenttää kartoittamalla, olisiko musiikkimaalausta oppimismenetelmänä tarpeen hyödyntää koulumaailmassa enemmän. Musiikkimaalauksella tarkoitetaan menetelmää, jossa kuunneltavaa musiikkia pyritään ilmaisemaan kuvallisessa muodossa, esimerkiksi tämän tutkimuksen kohdalla vesiväreillä maalaten. Musiikkimaalausta menetelmänä voidaan pitää lapsilähtöisenä ja kokemuksellisena. Teoreettisen viitekehyksen alussa esitelläänkin sekä lapsilähtöisyyttä että kokemuksellisuutta hieman tarkemmin. Koska musiikkimaalauksessa yhdistyvät musiikki ja kuvataide, teoreettisessa viitekehyksessä avataan myös integraation käsitettä ja sen eri käyttöyhteyksiä. Teoreettisen viitekehyksen lopussa tarkastelun kohteena on musiikilliseen ja kuvataiteelliseen kehitykseen liittyvät kolme mallia, jotka ovat Swanwickin ja Tillmanin musiikillisen kehityksen malli, Lowenfeldin kuvallisen ilmaisun kehitysvaiheisiin liittyvä malli sekä Hargreavesin ja Galtonin taiteellisen kehityksen malli. Tutkimukseni aineistonkeruu tapahtui eräässä Pohjois-Pohjanmaalla sijaitsevassa koulussa kolmen oppitunnin mittaisessa tuokiossa, johon osallistui yhteensä 13 oppilasta. Kokonaisuus sisälsi kolmen harjoituksen mittaisen musiikkimaalauskokonaisuuden, kyselylomakkeisiin vastaamisen musiikkimaalausta ennen ja sen jälkeen sekä neljän oppilaan puolistrukturoidut teemahaastattelut. Haastattelut pohjautuivat suurelta osin kyselylomakevastauksiin. Tutkimukseni aineisto koostuu siis sekä kyselylomakevastauksista että haastatteluista. Kyselylomakkeet ovat kuitenkin tutkimuksen keskeisin aineistonkeruumenetelmä, kun taas haastattelut toimivat lähinnä tutkimuksen kannalta olennaista lisätietoa antavana ja kyselylomakevastauksia täydentävänä aineistonkeruumenetelmänä. Koska tutkimuksen tavoitteena on tarkastella oppilaiden erilaisia käsityksiä tutkittavasta aiheesta, tutkimuksen metodologia rakentuu fenomenografisen tutkimusotteen pohjalle. Fenomenografiselle tutkimukselle tyypillistä on, että aineistosta etsitään erilaisia näkökulmia, joista muodostetaan erillisiä kategorioita. Tutkimukseni aineiston analyysin aluksi poimin koko aineistosta tutkimuksen kannalta olennaiset seikat ja sijoittelin ne kyselylomakkeiden mukaisesti eri kysymysten alle. Tämän jälkeen muodostin vastauksista fenomenografisen tutkimuksen mukaisesti merkityskategorioita. Merkityskategoriat rakentuivat niiden perusteluiden ympärille, joita oppilaat olivat käyttäneet kertoessaan musiikkimaalauskokemuksistaan. Lopuksi vertailin oppilaiden vastauksia ennen musiikkimaalaustuokiota ja tuokion jälkeen. Tällöin pyrkimyksenäni oli löytää vastauksista yhtäläisyyksiä ja eroja. Oppilaat kokivat musiikkimaalauksen pääasiassa positiiviseksi kokemukseksi sekä ennen musiikkimaalaustuokiota että tuokion jälkeen esimerkiksi siksi, että se viehätti heitä uutena ja perinteisestä maalaamisesta poikkeavana työtapana. Toisaalta jotkut oppilaan kuvailivat musiikkimaalaustuokiota haastavaksi tai tuntemuksiaan pelonsekaisen jännityksen kaltaisiksi siitä syystä, että musiikkimaalaus oli työtapana uusi. Suhteessa oppimiseensa oppilaat kertoivat musiikkimaalauksen esimerkiksi auttaneen heitä keskittymään enemmän maalaamiseen, käyttämään rohkeammin mielikuvitustaan ja kuuntelemaan musiikkia tarkemmin. Kaiken kaikkiaan tulosten perusteella voidaan todeta, että oppilaat kokivat musiikkimaalaustuokion tukeneen heidän oppimistaan monin eri tavoin. Tästä syystä musiikkimaalausta voisi oppilaiden näkökulmasta ajatellen ehdottomasti harkita perinteistä maalausta tukevaksi työtavaksi koulumaailmaan. Koska tutkimukseni toteutettiin melko pienelle tutkimusjoukolle (13 oppilasta), tutkimustuloksia ei voi kovinkaan laajalti yleistää. Toisaalta muutoin tutkimukseni toteutus onnistui luotettavasti ja kaikin puolin hyvin, joten tulokset toimivat varmasti suuntaa-antavina jatkotutkimusta ajatellen. Jatkotutkimusta voisi tehdä esimerkiksi toteuttamalla musiikkimaalausta eri tekniikoin tai musiikkimaalausharjoittein. Eräs jatkotutkimuksen mahdollisuus olisi myös se, että tutkimuksen kohderyhmänä olisi vanhemmat lapset, esimerkiksi yläkoulu- tai lukioikäiset. Tällä tavoin saataisiin informaatiota siitä, olisiko musiikkimaalaukselle sijaa myös vanhempien ikäryhmien opetuksessa.
- Published
- 2014
17. Does long in vitro culture promote large for gestational age babies?
- Author
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Makinen, S., primary, Soderstrom-Anttila, V., additional, Vainio, J., additional, Suikkari, A.- M., additional, and Tuuri, T., additional
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- 2012
- Full Text
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18. SESSION 48: CULTURE, CRYO AND COCHRANE
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Koike, A., primary, Fukuda, A., additional, Sugihara, K., additional, Haruki, A., additional, Morimoto, Y., additional, Kleijkers, S. H. M., additional, Van Montfoort, A. P. A., additional, Smits, L. J. M., additional, Viechtbauer, W., additional, Roseboom, T. J., additional, Nelissen, E. C. M., additional, Coonen, E., additional, Derhaag, J. G., additional, Bastings, L., additional, Schreurs, I. E. L., additional, Evers, J. L. H., additional, Dumoulin, J. C. M., additional, Tuuri, T., additional, Makinen, S., additional, Soderstrom-Anttila, V., additional, Vainio, J., additional, Suikkari, A. M., additional, Wang, Y. A., additional, Sullivan, E. A., additional, Farquhar, C., additional, Popovich, I., additional, Windsor, B., additional, Jordan, V., additional, and Shea, B., additional
- Published
- 2012
- Full Text
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19. Follicles are found in the ovaries of adolescent girls with Turner'ssyndrome.
- Author
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Hreinsson, JG, Otala, M, Fridstrom, M, Borgstrom, B, Rasmussen, C, Lundqvist, M, Tuuri, T, Simberg, N, Mikkola, M, Dunkel, L, Hovatta, O, Hreinsson, JG, Otala, M, Fridstrom, M, Borgstrom, B, Rasmussen, C, Lundqvist, M, Tuuri, T, Simberg, N, Mikkola, M, Dunkel, L, and Hovatta, O
- Published
- 2002
20. The effects of insulin, and insulin-like growth factors I and II on human ovarian follicles in long-term culture
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Louhio, H., primary, Hovatta, O., additional, Sjoberg, J., additional, and Tuuri, T., additional
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- 2000
- Full Text
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21. P-109. Comparison of two recombinant follicle stimulating hormone preparations in in-vitro fertilization treatment: results from a randomized study
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Tulppala, M., primary, Aho, M., additional, Tuuri, T., additional, Vilska, S., additional, Foudila, F., additional, Hakala-Ala-Pietilä, T., additional, Moilanen, J., additional, Bützow, T., additional, Kaukoranta, S., additional, Söderstrom-Anttila, V., additional, Siegberg, R., additional, and Hovatta, O., additional
- Published
- 1999
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22. Testicular biopty gun needle biopsy in collecting spermatozoa for intracytoplasmic injection, cryopreservation and histology
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Tuuri, T., primary
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- 1999
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23. Identification of ovarian granulosa cells as a novel site of expression for bone morphogenetic protein-3 (BMP-3/osteogenin) and regulation of BMP-3 messenger ribonucleic acids by chorionic gonadotropin in cultured human granulosa-luteal cells.
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Jaatinen, R, primary, Rosen, V, additional, Tuuri, T, additional, and Ritvos, O, additional
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- 1996
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24. Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor
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Hilden, K, primary, Tuuri, T, additional, Eramaa, M, additional, and Ritvos, O, additional
- Published
- 1994
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25. Cell death and its suppression in human ovarian tissue culture.
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Otala, M., Erkkilä, K., Tuuri, T., Sjöberg, J., Suomalainen, L., Suikkari, A-M., Pentikäinen, V., and Dunkel, L.
- Published
- 2002
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26. The predictive value of pronuclear morphology of zygotes in the assessment of human embryo quality.
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Salumets, Andres, Hydén-Granskog, Christel, Suikkari, Anne-Maria, Tiitinen, Aila, Tuuri, Timo, Salumets, A, Hydén-Granskog, C, Suikkari, A M, Tiitinen, A, and Tuuri, T
- Abstract
Background: Recent studies have shown that zygote morphology could be used for the assessment of human embryo quality. Pronuclear (PN) morphology is based on certain distinct features seen in zygotes 16-18 h after fertilization. In the present study PN stage morphology was assessed and combined with a single embryo transfer in order to investigate whether currently used zygote classifications are able to predict embryo quality and implantation rates.Methods and Results: Zygotes were analysed according to two different classification systems. In the first, a total of 764 zygotes was analysed according to the degree of polarization of nucleolar precursor bodies (NPB). Zygotes with unpolarized PN (i.e. scattered localization of NPB) showed significantly slower (P < 0.005) cleavage rates (38.9%) than zygotes having at least one pronucleus polarized (57.3% and 54%). However, there was no difference in the pregnancy rate in 105 single embryo transfers between the groups. The appearance of a cytoplasmic halo was related to embryo morphology. Embryos derived from halo-positive zygotes had significantly better (P < 0.05) morphology (60.9%) compared to halo-negative derived embryos (52.2%), but in terms of pregnancy rates no difference was found. A total of 1520 zygotes was analysed according to a second classification system, which was based on the number and distribution of NPB. In the comparative analysis, none of the six different classes produced superior quality embryos or higher pregnancy rates in 144 single embryo transfers.Conclusions: Our results indicate that there are no significant differences in embryo quality or implantation/pregnancy rates between proposed zygote classes. [ABSTRACT FROM AUTHOR]- Published
- 2001
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27. Luteal phase start of low-dose FSH priming of follicles results in an efficient recovery, maturation and fertilization of immature human oocytes.
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Suikkari, Anne-Maria, Tulppala, Maija, Tuuri, Timo, Hovatta, Outi, Barnes, Frank, Suikkari, A M, Tulppala, M, Tuuri, T, Hovatta, O, and Barnes, F
- Abstract
In this prospective study we investigated whether the maturation and fertilization of immature oocytes can be improved by administration of recombinant follicle stimulating hormone (rFSH) starting in the late luteal phase in two groups of women: group 1 (n = 6) women with regular menstrual cycles; and group 2 (n = 6) women with irregular cycles and polycystic ovaries (PCO) on ultrasound examination. Low-dose (37.5 IU) rFSH was commenced 11 days after LH surge during a spontaneous menstrual cycle and on the ninth day of progesterone administration in an irregular cycle. Recombinant FSH was continued until the leading follicle was approximately 10 mm in diameter. The oocytes were retrieved after withdrawing rFSH for 2-5 days. In total, 136 oocytes were recovered (group 1, 67 oocytes; group 2, 69 oocytes). Nine of the oocytes from PCO women were atretic at retrieval. Oocytes complete with cumulus cells were cultured for 44 h in complex tissue culture medium supplemented with gonadotrophins and fetal calf serum. After maturation, the cumulus cells were removed and metaphase II oocytes were injected with spermatozoa. Respectively, the oocyte maturation and fertilization rates were 64 and 72% in group 1, and 78 and 57% in group 2 (not significant). After fertilization, the zygotes (group 1, n = 22; group 2, n = 11) and cleavage stage embryos (group 1, n = 9; group 2, n = 15) were frozen in propanediol. All women except one (11/12) had approximately five zygotes or cleaved embryos frozen. The viability of in-vitro matured frozen-thawed embryos was generally poorer than that (81%) seen after conventional intracytoplasmic sperm injection, with 61% survival in group 1 and 23% in group 2. Fifteen embryo transfers resulted in one miscarriage at 6 weeks gestation. The late luteal start of low-dose rFSH yielded a good number of immature oocytes in women with both regular and irregular cycles. Two out of three of these oocytes matured and fertilized. However, cryosurvival of the zygotes and cleaved embryos was unsatisfactory and thus cryopreservation of in-vitro matured embryos may not be an optimal procedure. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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28. Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study.
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Tulppala, M, Aho, M, Tuuri, T, Vilska, S, Foudila, T, Hakala-Ala-Pietilä, T, Moilanen, J, Bützow, T, Kaukoranta, S, Söderström-Anttila, V, Siegberg, R, Suikkari, A M, and Hovatta, O
- Subjects
INFERTILITY treatment ,CLINICAL trials ,COMPARATIVE studies ,EMBRYO transfer ,FERTILIZATION in vitro ,FOLLICLE-stimulating hormone ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,INDUCED ovulation ,RECOMBINANT proteins ,RESEARCH ,EVALUATION research ,RANDOMIZED controlled trials ,OVARIAN hyperstimulation syndrome ,THERAPEUTICS - Abstract
A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F and Puregon) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22-43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F n = 164, Puregon n = 158 or 300 IU/day: Gonal-F n = 8, Puregon n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon (150 IU/day). The ongoing cumulative pregnancy rates after frozen-thawed embryo transfer were 35.4% with Gonal-F and 37.7% with Puregon. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F, 2.0% and Puregon, 0.7%) were also similar. Gonal-F and Puregon were equally and highly effective in stimulation for IVF and ICSI. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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29. The N-glycome of human embryonic stem cells
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Olonen Anne, Aitio Olli, Jaatinen Taina, Tiittanen Minna, Blomqvist Maria, Olsson Cia, Mikkola Milla, Heiskanen Annamari, Satomaa Tero, Helin Jari, Hiltunen Jukka, Natunen Jari, Tuuri Timo, Otonkoski Timo, Saarinen Juhani, and Laine Jarmo
- Subjects
Cytology ,QH573-671 - Abstract
Abstract Background Complex carbohydrate structures, glycans, are essential components of glycoproteins, glycolipids, and proteoglycans. While individual glycan structures including the SSEA and Tra antigens are already used to define undifferentiated human embryonic stem cells (hESC), the whole spectrum of stem cell glycans has remained unknown. We undertook a global study of the asparagine-linked glycoprotein glycans (N-glycans) of hESC and their differentiated progeny using MALDI-TOF mass spectrometric and NMR spectroscopic profiling. Structural analyses were performed by specific glycosidase enzymes and mass spectrometric fragmentation analyses. Results The data demonstrated that hESC have a characteristic N-glycome which consists of both a constant part and a variable part that changes during hESC differentiation. hESC-associated N-glycans were downregulated and new structures emerged in the differentiated cells. Previously mouse embryonic stem cells have been associated with complex fucosylation by use of SSEA-1 antibody. In the present study we found that complex fucosylation was the most characteristic glycosylation feature also in undifferentiated hESC. The most abundant complex fucosylated structures were Lex and H type 2 antennae in sialylated complex-type N-glycans. Conclusion The N-glycan phenotype of hESC was shown to reflect their differentiation stage. During differentiation, hESC-associated N-glycan features were replaced by differentiated cell-associated structures. The results indicated that hESC differentiation stage can be determined by direct analysis of the N-glycan profile. These results provide the first overview of the N-glycan profile of hESC and form the basis for future strategies to target stem cell glycans.
- Published
- 2009
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30. Activin disrupts epithelial branching morphogenesis in developing glandular organs of the mouse
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Ritvos, O., Tuuri, T., Eraemaa, M., and Sainio, K.
- Published
- 1995
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31. In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity.
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Rooda I, Hassan J, Hao J, Wagner M, Moussaud-Lamodière E, Jääger K, Otala M, Knuus K, Lindskog C, Papaikonomou K, Gidlöf S, Langenskiöld C, Vogt H, Frisk P, Malmros J, Tuuri T, Salumets A, Jahnukainen K, Velthut-Meikas A, and Damdimopoulou P
- Subjects
- Female, Humans, Adult, Child, Oocytes metabolism, MicroRNAs genetics, MicroRNAs metabolism, Gene Expression Profiling, Cyclophosphamide, Cryopreservation, Fertility Preservation methods, Adolescent, Signal Transduction, Child, Preschool, Ovarian Follicle metabolism, Transcriptome
- Abstract
The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages., (© 2024. The Author(s).)
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- 2024
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32. The intensities of vowels and plosive bursts and their impact on text intelligibility in singinga).
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Vurma A, Meister E, Meister L, Ross J, Raju M, Kala V, and Dede T
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- Humans, Cognition, Recognition, Psychology, Software, Acoustics, Singing
- Abstract
In classical singing, there are often problems with the intelligibility of sung text. The present study aims to test the hypotheses that (1) in loud operatic singing, compared with speaking, the intensity of voiceless plosives increases less than the intensity of vowels, leading to poorer recognition of plosives; and (2) pronouncing the plosive bursts with greater intensity improves their recognition. The acoustic analysis of nine opera arias in Italian from the Classical and Romantic periods performed by ten classically trained singers showed that the average difference in the intensity of vowels when sung and spoken was 14.6 dB [standard deviation (SD) = 7.2 dB], while the difference in the intensity of voiceless plosive bursts was only 6.6 dB (SD = 6 dB). In a perception test with 73 participants, increasing the intensity of the plosive bursts generally improved the recognition of plosives in the sung /a-plosive-a/ sequences, but mainly when reverberation and/or pink noise imitating instrumental accompaniments were added to the stimuli. At the same time, recognition of plosives was often better than chance even when the plosive burst was missing and replaced by silence., (© 2023 Acoustical Society of America.)
- Published
- 2023
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33. CRISPR/Cas9-mediated activation of NR5A1 steers female human embryonic stem cell-derived bipotential gonadal-like cells towards a steroidogenic cell fate.
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Danti L, Lundin K, Sepponen K, Yohannes DA, Kere J, Tuuri T, and Tapanainen JS
- Subjects
- Animals, Humans, Female, Male, CRISPR-Cas Systems, Steroidogenic Factor 1 genetics, Cell Differentiation genetics, Cytochrome P450 Family 17, Human Embryonic Stem Cells
- Abstract
The nuclear receptor subfamily 5 group A member 1 (NR5A1), encoding steroidogenic factor 1 (SF-1), has been identified as a critical factor in gonadal development in animal studies. A previous study of ours suggested that upregulation of NR5A1 during early gonadal differentiation in male (46,XY) human pluripotent stem cells steers the cells into a more mature gonadal cell type. However, the detailed role of NR5A1 in female gonadal differentiation has yet to be determined. In this study, by combining the processes of gonadal differentiation and conditional gene activation, we show that NR5A1 induction predominantly upregulates the female gonadal marker inhibin subunit α (INHA) and steroidogenic markers steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 17 subfamily A member 1 (CYP17A1), hydroxy-delta-5-steroid dehydrogenase (HSD3B2) and hydroxysteroid 17-beta dehydrogenase 1 (HSD17B1). In contrast, NR5A1 induction did not seem to affect the bipotential gonadal markers gata binding protein 4 (GATA4) and Wilms' tumour suppressor 1 (WT1) nor the female gonadal markers r-spondin 1 (RSPO1) and wnt family member 4 (WNT4). Differentially expressed genes were highly associated with adrenal and ovarian steroidogenesis pathways. Moreover, time-series analysis revealed different dynamic changes between male and female induced samples, where continuously upregulated genes in female gonadal differentiation were mostly associated with adrenal steroidogenesis. Thus, in contrast to male gonadal differentiation, NR5A1 is necessary but not sufficient to steer human embryonic stem cell (hESC)-derived bipotential gonadal-like cells towards a more mature somatic, female cell fate. Instead, it seems to direct bipotential gonadal-like cells more towards a steroidogenic-like cell population. The information obtained in this study helps in elucidating the role of NR5A1 in gonadal differentiation of a female stem cell line., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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34. FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner.
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Yellapragada V, Eskici N, Wang Y, Madhusudan S, Vaaralahti K, Tuuri T, and Raivio T
- Subjects
- Fibroblast Growth Factor 8 metabolism, Fibroblast Growth Factor 8 pharmacology, Forkhead Transcription Factors metabolism, Humans, Intracellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, Nerve Tissue Proteins metabolism, Neurogenesis, Neurons metabolism, Gonadotropin-Releasing Hormone metabolism, Gonadotropin-Releasing Hormone pharmacology, Receptor, Fibroblast Growth Factor, Type 1 genetics, Receptor, Fibroblast Growth Factor, Type 1 metabolism
- Abstract
Fibroblast growth factor 8 (FGF8), acting through the fibroblast growth factor receptor 1 (FGFR1), has an important role in the development of gonadotropin-releasing hormone-expressing neurons (GnRH neurons). We hypothesized that FGF8 regulates differentiation of human GnRH neurons in a time- and dose-dependent manner via FGFR1. To investigate this further, human pluripotent stem cells were differentiated during 10 days of dual-SMAD inhibition into neural progenitor cells, followed either by treatment with FGF8 at different concentrations (25 ng/ml, 50 ng/ml or 100 ng/ml) for 10 days or by treatment with 100 ng/ml FGF8 for different durations (2, 4, 6 or 10 days); cells were then matured through DAPT-induced inhibition of Notch signaling for 5 days into GnRH neurons. FGF8 induced expression of GNRH1 in a dose-dependent fashion and the duration of FGF8 exposure correlated positively with gene expression of GNRH1 (P<0.05, Rs=0.49). However, cells treated with 100 ng/ml FGF8 for 2 days induced the expression of genes, such as FOXG1, ETV5 and SPRY2, and continued FGF8 treatment induced the dynamic expression of several other genes. Moreover, during exposure to FGF8, FGFR1 localized to the cell surface and its specific inhibition with the FGFR1 inhibitor PD166866 reduced expression of GNRH1 (P<0.05). In neurons, FGFR1 also localized to the nucleus. Our results suggest that dose- and time-dependent FGF8 signaling via FGFR1 is indispensable for human GnRH neuron ontogeny. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)
- Published
- 2022
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35. DUX4 is a multifunctional factor priming human embryonic genome activation.
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Vuoristo S, Bhagat S, Hydén-Granskog C, Yoshihara M, Gawriyski L, Jouhilahti EM, Ranga V, Tamirat M, Huhtala M, Kirjanov I, Nykänen S, Krjutškov K, Damdimopoulos A, Weltner J, Hashimoto K, Recher G, Ezer S, Paluoja P, Paloviita P, Takegami Y, Kanemaru A, Lundin K, Airenne TT, Otonkoski T, Tapanainen JS, Kawaji H, Murakawa Y, Bürglin TR, Varjosalo M, Johnson MS, Tuuri T, Katayama S, and Kere J
- Abstract
Double homeobox 4 ( DUX4 ) is expressed at the early pre-implantation stage in human embryos. Here we show that induced human DUX4 expression substantially alters the chromatin accessibility of non-coding DNA and activates thousands of newly identified transcribed enhancer-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation of transcribed enhancers by C-terminal DUX4 motifs results in the increased expression of target embryonic genome activation (EGA) genes ZSCAN4 and KHDC1P1 . We show that DUX4 is markedly enriched in human zygotes, followed by intense nuclear DUX4 localization preceding and coinciding with minor EGA. DUX4 knockdown in human zygotes led to changes in the EGA transcriptome but did not terminate the embryos. We also show that the DUX4 protein interacts with the Mediator complex via the C-terminal KIX binding motif. Our findings contribute to the understanding of DUX4 as a regulator of the non-coding genome., Competing Interests: Y.T. and A.K. are employees of K.K.DNAFORM. Y. T. and Y. M. are inventors on a patent related to NET-CAGE technology., (© 2022 The Authors.)
- Published
- 2022
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36. A blueprint of the topology and mechanics of the human ovary for next-generation bioengineering and diagnosis.
- Author
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Ouni E, Peaucelle A, Haas KT, Van Kerk O, Dolmans MM, Tuuri T, Otala M, and Amorim CA
- Subjects
- Adult, Age Factors, Aged, Bioengineering, Child, Child, Preschool, Elastic Tissue anatomy & histology, Elastic Tissue metabolism, Elasticity, Extracellular Matrix chemistry, Extracellular Matrix metabolism, Female, Hormones metabolism, Humans, Middle Aged, Ovarian Follicle growth & development, Ovarian Reserve, Ovary cytology, Viscosity, Young Adult, Ovary anatomy & histology, Ovary physiology
- Abstract
Although the first dissection of the human ovary dates back to the 17
th century, the biophysical characteristics of the ovarian cell microenvironment are still poorly understood. However, this information is vital to deciphering cellular processes such as proliferation, morphology and differentiation, as well as pathologies like tumor progression, as demonstrated in other biological tissues. Here, we provide the first readout of human ovarian fiber morphology, interstitial and perifollicular fiber orientation, pore geometry, topography and surface roughness, and elastic and viscoelastic properties. By determining differences between healthy prepubertal, reproductive-age, and menopausal ovarian tissue, we unravel and elucidate a unique biophysical phenotype of reproductive-age tissue, bridging biophysics and female fertility. While these data enable to design of more biomimetic scaffolds for the tissue-engineered ovary, our analysis pipeline is applicable for the characterization of other organs in physiological or pathological states to reveal their biophysical markers or design their bioinspired analogs., (© 2021. The Author(s).)- Published
- 2021
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37. Small RNA expression and miRNA modification dynamics in human oocytes and early embryos.
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Paloviita P, Hydén-Granskog C, Yohannes DA, Paluoja P, Kere J, Tapanainen JS, Krjutškov K, Tuuri T, Võsa U, and Vuoristo S
- Subjects
- Embryo, Mammalian metabolism, Humans, Oocytes metabolism, Sequence Analysis, RNA methods, Zygote metabolism, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
Small noncoding RNAs (sRNAs) play important roles during the oocyte-to-embryo transition (OET), when the maternal phenotype is reprogrammed and the embryo genome is gradually activated. The transcriptional program driving early human development has been studied with the focus mainly on protein-coding RNAs, and expression dynamics of sRNAs remain largely unexplored. We profiled sRNAs in human oocytes and early embryos using an RNA-sequencing (RNA-seq) method suitable for low inputs of material. We show that OET in humans is temporally coupled with the transition from predominant expression of oocyte short piRNAs (os-piRNAs) in oocytes, to activation of microRNA (miRNA) expression in cleavage stage embryos. Additionally, 3' mono- and oligoadenylation of miRNAs is markedly increased in zygotes. We hypothesize that this may modulate the function or stability of maternal miRNAs, some of which are retained throughout the first cell divisions in embryos. This study is the first of its kind elucidating the dynamics of sRNA expression and miRNA modification along a continuous trajectory of early human development and provides a valuable data set for in-depth interpretative analyses., (© 2021 Paloviita et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2021
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38. Characterization of the human GnRH neuron developmental transcriptome using a GNRH1 -TdTomato reporter line in human pluripotent stem cells.
- Author
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Lund C, Yellapragada V, Vuoristo S, Balboa D, Trova S, Allet C, Eskici N, Pulli K, Giacobini P, Tuuri T, and Raivio T
- Subjects
- CRISPR-Associated Protein 9 metabolism, CRISPR-Cas Systems genetics, Cell Line, Fetus cytology, Fibroblast Growth Factor 8 pharmacology, Humans, Hypogonadism genetics, LIM-Homeodomain Proteins metabolism, Neurons drug effects, Pluripotent Stem Cells drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Transcription Factors metabolism, Up-Regulation drug effects, Up-Regulation genetics, Genes, Reporter, Gonadotropin-Releasing Hormone metabolism, Neurons metabolism, Pluripotent Stem Cells metabolism, Transcriptome genetics
- Abstract
Gonadotropin-releasing hormone (GnRH) neurons provide a fundamental signal for the onset of puberty and subsequent reproductive functions by secretion of gonadotropin-releasing hormone. Their disrupted development or function leads to congenital hypogonadotropic hypogonadism (CHH). To model the development of human GnRH neurons, we generated a stable GNRH1 -TdTomato reporter cell line in human pluripotent stem cells (hPSCs) using CRISPR-Cas9 genome editing. RNA-sequencing of the reporter clone, differentiated into GnRH neurons by dual SMAD inhibition and FGF8 treatment, revealed 6461 differentially expressed genes between progenitors and GnRH neurons. Expression of the transcription factor ISL1 , one of the top 50 most upregulated genes in the TdTomato-expressing GnRH neurons, was confirmed in 10.5 gestational week-old human fetal GnRH neurons. Among the differentially expressed genes, we detected 15 genes that are implicated in CHH and several genes that are implicated in human puberty timing. Finally, FGF8 treatment in the neuronal progenitor pool led to upregulation of 37 genes expressed both in progenitors and in TdTomato-expressing GnRH neurons, which suggests upstream regulation of these genes by FGF8 signaling during GnRH neuron differentiation. These results illustrate how hPSC-derived human GnRH neuron transcriptomic analysis can be utilized to dissect signaling pathways and gene regulatory networks involved in human GnRH neuron development.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)
- Published
- 2020
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39. Complement in Human Pre-implantation Embryos: Attack and Defense.
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Reichhardt MP, Lundin K, Lokki AI, Recher G, Vuoristo S, Katayama S, Tapanainen JS, Kere J, Meri S, and Tuuri T
- Subjects
- Gene Expression Regulation, Developmental, Humans, Microscopy, Confocal, Sequence Analysis, RNA, Single-Cell Analysis, Complement System Proteins immunology, Embryo, Mammalian immunology, Embryonic Development immunology
- Abstract
It is essential for early human life that mucosal immunological responses to developing embryos are tightly regulated. An imbalance of the complement system is a common feature of pregnancy complications. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus, far, immunological imbalance has been considered in stages of pregnancy following implantation. We here show that complement activation against developing human embryos takes place already at the pre-implantation stage. Using confocal microscopy, we observed deposition of activation products on healthy developing embryos, which highlights the need for strict complement regulation. We show that embryos express complement membrane inhibitors and bind soluble regulators. These findings show that mucosal complement targets human embryos, and indicate potential adverse pregnancy outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing revealed cellular expression of complement activators. This shows that the embryonic cells themselves have the capacity to express and activate C3 and C5. The specific local embryonic expression of complement components, regulators, and deposition of activation products on the surface of embryos suggests that complement has immunoregulatory functions and furthermore may impact cellular homeostasis and differentiation at the earliest stages of life., (Copyright © 2019 Reichhardt, Lundin, Lokki, Recher, Vuoristo, Katayama, Tapanainen, Kere, Meri and Tuuri.)
- Published
- 2019
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40. MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression.
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Yellapragada V, Liu X, Lund C, Känsäkoski J, Pulli K, Vuoristo S, Lundin K, Tuuri T, Varjosalo M, and Raivio T
- Abstract
Paternally-inherited loss-of-function mutations in makorin ring finger protein 3 gene ( MKRN3 ) underlie central precocious puberty. To investigate the puberty-related mechanism(s) of MKRN3 in humans, we generated two distinct bi-allelic MKRN3 knock-out human pluripotent stem cell lines, Del 1 and Del 2, and differentiated them into GNRH1 -expressing neurons. Both Del 1 and Del 2 clones could be differentiated into neuronal progenitors and GNRH1 -expressing neurons, however, the relative expression of GNRH1 did not differ from wild type cells ( P = NS). Subsequently, we investigated stable and dynamic protein-protein interaction (PPI) partners of MKRN3 by stably expressing it in HEK cells followed by mass spectrometry analyses. We found 81 high-confidence novel protein interaction partners, which are implicated in cellular processes such as insulin signaling, RNA metabolism and cell-cell adhesion. Of the identified interactors, 20 have been previously implicated in puberty timing. In conclusion, our stem cell model for generation of GNRH1 -expressing neurons did not offer mechanistic insight for the role of MKRN3 in puberty initiation. The PPI data, however, indicate that MKRN3 may regulate puberty by interacting with other puberty-related proteins. Further studies are required to elucidate the possible mechanisms and outcomes of these interactions.
- Published
- 2019
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41. Demographic and evolutionary trends in ovarian function and aging.
- Author
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Laisk T, Tšuiko O, Jatsenko T, Hõrak P, Otala M, Lahdenperä M, Lummaa V, Tuuri T, Salumets A, and Tapanainen JS
- Subjects
- Animals, Cellular Senescence physiology, Demography, Female, Humans, Menopause physiology, Ovarian Reserve physiology, Reproduction physiology, Aging physiology, Biological Evolution, Ovary physiology
- Abstract
Background: The human female reproductive lifespan is regulated by the dynamics of ovarian function, which in turn is influenced by several factors: from the basic molecular biological mechanisms governing folliculogenesis, to environmental and lifestyle factors affecting the ovarian reserve between conception and menopause. From a broader point of view, global and regional demographic trends play an additional important role in shaping the female reproductive lifespan, and finally, influences on an evolutionary scale have led to the reproductive senescence that precedes somatic senescence in humans., Objective and Rationale: The narrative review covers reproductive medicine, by integrating the molecular mechanisms of ovarian function and aging with short-term demographic and long-term evolutionary trends., Search Methods: PubMed and Google Scholar searches were performed with relevant keywords (menopause, folliculogenesis, reproductive aging, reproductive lifespan and life history theory). The reviewed articles and their references were restricted to those written in English., Outcomes: We discuss and summarize the rapidly accumulating information from large-scale population-based and single-reproductive-cell genomic studies, their constraints and advantages in the context of female reproductive aging as well as their possible evolutionary significance on the life history trajectory from foetal-stage folliculogenesis until cessation of ovarian function in menopause. The relevant environmental and lifestyle factors and demographic trends are also discussed in the framework of predominant evolutionary hypotheses explaining the origin and maintenance of menopause., Wider Implications: The high speed at which new data are generated has so far raised more questions than it has provided solid answers and has been paralleled by a lack of satisfactory interpretations of the findings in the context of human life history theory. Therefore, the recent flood of data could offer an unprecedented tool for future research to possibly confirm or rewrite human evolutionary reproductive history, at the same time providing novel grounds for patient counselling and family planning strategies.
- Published
- 2019
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42. rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology.
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Marjonen H, Auvinen P, Kahila H, Tšuiko O, Kõks S, Tiirats A, Viltrop T, Tuuri T, Söderström-Anttila V, Suikkari AM, Salumets A, Tiitinen A, and Kaminen-Ahola N
- Subjects
- Adult, Binding Sites, CCCTC-Binding Factor metabolism, Case-Control Studies, Estonia, Female, Finland, Genotype, Humans, Infant, Newborn, Insulin-Like Growth Factor II genetics, Male, Maternal Age, Placenta chemistry, Pregnancy, RNA, Long Noncoding chemistry, RNA, Long Noncoding metabolism, Reproductive Techniques, Assisted, Birth Weight genetics, DNA Methylation, Genomic Imprinting, Polymorphism, Single Nucleotide, RNA, Long Noncoding genetics
- Abstract
Background: Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 ( IGF2 )/ H19 locus known to be important for normal growth. This locus is regulated by H19 imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF, associates with a genotype-specific trend to the DNA methylation. Due to this association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18 ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously conceived pregnancies as controls were recruited in Finland and Estonia for genotype-specific examination. DNA methylation levels at the H19 ICR, H19 DMR, and long interspersed nuclear elements in placental tissue were explored by MassARRAY EpiTYPER ( n = 122). Allele-specific changes in the methylation level of H19 ICR in placental tissue ( n = 26) and white blood cells (WBC, n = 8) were examined by bisulfite sequencing. Newborns' ( n = 243) anthropometrics was analyzed by using international growth standards., Results: A consistent trend of genotype-specific decreased methylation level was observed in paternal allele of rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A genotype, at H19 ICR in ART placentas. This hypomethylation was not detected in WBCs. Also genotype-specific differences in FRESH-derived newborns' birth weight and head circumference were observed ( P = 0.04, P = 0.004, respectively): FRESH-derived newborns with G/G genotype were heavier ( P = 0.04) and had larger head circumference ( P = 0.002) compared to newborns with A/A genotype. Also, the placental weight and birth weight of controls, FRESH- and FET-derived newborns differed significantly in rs10732516 A/A genotype ( P = 0.024, P = 0.006, respectively): the placentas and newborns of FET-derived pregnancies were heavier compared to FRESH-derived pregnancies ( P = 0.02, P = 0.004, respectively)., Conclusions: The observed DNA methylation changes together with the phenotypic findings suggest that rs10732516 polymorphism associates with the effects of ART in a parent-of-origin manner. Therefore, this polymorphism should be considered when the effects of environmental factors on embryonic development are studied., Competing Interests: The study was approved by the Ethics Committee of Helsinki University Central Hospital (386/13/03/03/2012 and 285/13/03/03/2013) and Research Ethics Committee of the University of Tartu (256/M-17). Informed consent was obtained from all participants.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2018
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43. The Role of Sequential BMP Signaling in Directing Human Embryonic Stem Cells to Bipotential Gonadal Cells.
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Sepponen K, Lundin K, Knuus K, Väyrynen P, Raivio T, Tapanainen JS, and Tuuri T
- Subjects
- Activins pharmacology, Bone Morphogenetic Protein 7 genetics, Bone Morphogenetic Proteins pharmacology, Cells, Cultured, Embryonic Stem Cells drug effects, Gene Expression Regulation drug effects, Gonads drug effects, Humans, Pyridines pharmacology, Pyrimidines pharmacology, Signal Transduction drug effects, Signal Transduction physiology, Wnt Signaling Pathway drug effects, Wnt Signaling Pathway genetics, Bone Morphogenetic Proteins physiology, Cell Differentiation drug effects, Cell Differentiation genetics, Embryonic Stem Cells physiology, Gonads cytology, Gonads physiology
- Abstract
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but because of a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed., Objective: To establish an in vitro method for studying differentiation of bipotential gonadal progenitors by using human embryonic stem cells (hESCs) and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation., Design: We tested 17 protocols using activin A, CHIR-99021, and varying durations of BMP-7 and the BMP inhibitor dorsomorphin. Activation of activin A, WNT, and BMP pathways was optimized to induce differentiation., Setting: Academic research laboratory., Main Outcomes Measures: Cell differentiation, gene expression, and flow cytometry., Results: The two most efficient protocols consistently upregulated IM markers LHX1, PAX2, and OSR1 at days 2 to 4 and bipotential gonadal markers EMX2, GATA4, WT1, and LHX9 at day 8 of culture. The outcome depended on the combination of the duration, concentration, and type of BMP activation and the length of WNT signaling. Adjusting any of the parameters substantially affected the requirements for other parameters., Conclusions: We have established a reproducible protocol for directed differentiation of hESCs into bipotential gonadal cells. The protocol can be used to model early gonadal development in humans and allows further differentiation to mature gonadal somatic cells., (Copyright © 2017 Endocrine Society)
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- 2017
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44. Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells.
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Lund C, Pulli K, Yellapragada V, Giacobini P, Lundin K, Vuoristo S, Tuuri T, Noisa P, and Raivio T
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- Cell Line, Cell Movement drug effects, Cell Proliferation drug effects, Fibroblast Growth Factor 8 pharmacology, Forkhead Transcription Factors metabolism, Humans, Nerve Tissue Proteins metabolism, Neural Stem Cells cytology, Neural Stem Cells drug effects, Neural Stem Cells metabolism, Neurons drug effects, Nose cytology, Pluripotent Stem Cells metabolism, Receptors, Notch metabolism, Smad Proteins antagonists & inhibitors, Smad Proteins metabolism, Gonadotropin-Releasing Hormone metabolism, Neurons cytology, Neurons metabolism, Pluripotent Stem Cells cytology
- Abstract
Gonadotropin-releasing hormone (GnRH) neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs) into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs) by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2016
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45. Selective microRNA-Offset RNA expression in human embryonic stem cells.
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Asikainen S, Heikkinen L, Juhila J, Holm F, Weltner J, Trokovic R, Mikkola M, Toivonen S, Balboa D, Lampela R, Icay K, Tuuri T, Otonkoski T, Wong G, and Hovatta O
- Subjects
- Base Sequence, Binding Sites, Cell Line, Computational Biology, Gene Expression Profiling, Gene Library, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs chemistry, Molecular Sequence Annotation, Molecular Sequence Data, RNA, Small Untranslated chemistry, Sequence Alignment, Gene Expression, Human Embryonic Stem Cells metabolism, MicroRNAs genetics, RNA, Small Untranslated genetics
- Abstract
Small RNA molecules, including microRNAs (miRNAs), play critical roles in regulating pluripotency, proliferation and differentiation of embryonic stem cells. miRNA-offset RNAs (moRNAs) are similar in length to miRNAs, align to miRNA precursor (pre-miRNA) loci and are therefore believed to derive from processing of the pre-miRNA hairpin sequence. Recent next generation sequencing (NGS) studies have reported the presence of moRNAs in human neurons and cancer cells and in several tissues in mouse, including pluripotent stem cells. In order to gain additional knowledge about human moRNAs and their putative development-related expression, we applied NGS of small RNAs in human embryonic stem cells (hESCs) and fibroblasts. We found that certain moRNA isoforms are notably expressed in hESCs from loci coding for stem cell-selective or cancer-related miRNA clusters. In contrast, we observed only sparse moRNAs in fibroblasts. Consistent with earlier findings, most of the observed moRNAs derived from conserved loci and their expression did not appear to correlate with the expression of the adjacent miRNAs. We provide here the first report of moRNAs in hESCs, and their expression profile in comparison to fibroblasts. Moreover, we expand the repertoire of hESC miRNAs. These findings provide an expansion on the known repertoire of small non-coding RNA contents in hESCs.
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- 2015
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46. Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells.
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Noisa P, Lund C, Kanduri K, Lund R, Lähdesmäki H, Lahesmaa R, Lundin K, Chokechuwattanalert H, Otonkoski T, Tuuri T, and Raivio T
- Subjects
- Cell Differentiation genetics, Gene Expression Regulation, Developmental physiology, Humans, Neural Crest metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Pluripotent Stem Cells metabolism, Receptors, Notch genetics, Receptors, Notch metabolism, SOXE Transcription Factors genetics, SOXE Transcription Factors metabolism, Signal Transduction physiology, Snail Family Transcription Factors, Transcription Factors genetics, Transcription Factors metabolism, Twist-Related Protein 1 genetics, Twist-Related Protein 1 metabolism, Cell Differentiation physiology, Neural Crest cytology, Pluripotent Stem Cells cytology
- Abstract
Neural crest cells are specified at the border between the neural plate and the epiderm. They are capable of differentiating into various somatic cell types, including craniofacial and peripheral nerve tissues. Notch signaling plays important roles during neurogenesis; however, its function during human neural crest development is poorly understood. Here, we generated self-renewing premigratory neural-crest-like cells (pNCCs) from human pluripotent stem cells (hPSCs) and investigated the roles of Notch signaling during neural crest differentiation. pNCCs expressed various neural-crest-specifier genes, including SLUG (also known as SNAI2), SOX10 and TWIST1, and were able to differentiate into most neural crest derivatives. Blocking Notch signaling during the pNCC differentiation suppressed the expression of neural-crest-specifier genes. By contrast, ectopic expression of activated Notch1 intracellular domain (NICD1) augmented the expression of neural-crest-specifier genes, and NICD1 was found to bind to their promoter regions. Notch activity was also required for the maintenance of the premigratory neural crest state, and the suppression of Notch signaling led to the generation of neural-crest-derived neurons. Taken together, we provide a protocol for the generation of pNCCs and show that Notch signaling regulates the formation, migration and differentiation of neural crest from hPSCs.
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- 2014
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47. A novel feeder-free culture system for human pluripotent stem cell culture and induced pluripotent stem cell derivation.
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Vuoristo S, Toivonen S, Weltner J, Mikkola M, Ustinov J, Trokovic R, Palgi J, Lund R, Tuuri T, and Otonkoski T
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- Cell Culture Techniques, Cell Differentiation, Cell Line, Choriocarcinoma genetics, Choriocarcinoma metabolism, Choriocarcinoma pathology, Embryonic Stem Cells, Extracellular Matrix metabolism, Feeder Cells, Hepatocytes cytology, Hepatocytes metabolism, Humans, Induced Pluripotent Stem Cells metabolism, Laminin metabolism, Neurons cytology, Neurons metabolism, Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells cytology, Pluripotent Stem Cells cytology
- Abstract
Correct interactions with extracellular matrix are essential to human pluripotent stem cells (hPSC) to maintain their pluripotent self-renewal capacity during in vitro culture. hPSCs secrete laminin 511/521, one of the most important functional basement membrane components, and they can be maintained on human laminin 511 and 521 in defined culture conditions. However, large-scale production of purified or recombinant laminin 511 and 521 is difficult and expensive. Here we have tested whether a commonly available human choriocarcinoma cell line, JAR, which produces high quantities of laminins, supports the growth of undifferentiated hPSCs. We were able to maintain several human pluripotent stem cell lines on decellularized matrix produced by JAR cells using a defined culture medium. The JAR matrix also supported targeted differentiation of the cells into neuronal and hepatic directions. Importantly, we were able to derive new human induced pluripotent stem cell (hiPSC) lines on JAR matrix and show that adhesion of the early hiPSC colonies to JAR matrix is more efficient than to matrigel. In summary, JAR matrix provides a cost-effective and easy-to-prepare alternative for human pluripotent stem cell culture and differentiation. In addition, this matrix is ideal for the efficient generation of new hiPSC lines.
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- 2013
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48. Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes.
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Velthut-Meikas A, Simm J, Tuuri T, Tapanainen JS, Metsis M, and Salumets A
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- Adult, Aromatase metabolism, Base Sequence, Cumulus Cells metabolism, Female, Gene Expression Profiling, Gene Ontology, Humans, MicroRNAs genetics, Molecular Sequence Annotation, Molecular Sequence Data, Receptors, FSH metabolism, Sequence Alignment, Signal Transduction genetics, Up-Regulation genetics, Aromatase genetics, Granulosa Cells enzymology, MicroRNAs metabolism, Receptors, FSH genetics, Sequence Analysis, RNA
- Abstract
The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signaling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and in vitro fertilization success. However, the posttranscriptional gene expression studies on micro-RNA (miRNA) level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the 2 intrafollicular somatic cell types: mural and cumulus granulosa cells (MGCs and CGCs, respectively) isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Altogether, 936 annotated and 9 novel miRNAs were identified. Ninety of the annotated miRNAs were differentially expressed between MGCs and CGCs. Bioinformatic prediction revealed that TGFβ, ErbB signaling, and heparan sulfate biosynthesis were targeted by miRNAs in both granulosa cell populations, whereas extracellular matrix remodeling, Wnt, and neurotrophin signaling pathways were enriched among miRNA targets in MGCs. Two of the nine novel miRNAs found were of intronic origin: one from the aromatase and the other from the FSH receptor gene. The latter miRNA was predicted to target the activin signaling pathway. In addition to revealing the genome-wide miRNA signature in human granulosa cells, our results suggest that posttranscriptional regulation of gene expression by miRNAs could play an important role in the modification of gonadotropin signaling. miRNA expression studies could therefore lead to new prognostic markers in assisted reproductive technologies.
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- 2013
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49. Molecular mechanisms of pluripotency and reprogramming.
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Na J, Plews J, Li J, Wongtrakoongate P, Tuuri T, Feki A, Andrews PW, and Unger C
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- Animals, Cell Differentiation, Cellular Reprogramming, DNA Damage genetics, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Homeodomain Proteins metabolism, Humans, Mice, MicroRNAs genetics, MicroRNAs metabolism, Nanog Homeobox Protein, Neoplastic Stem Cells cytology, Neoplastic Stem Cells metabolism, Octamer Transcription Factor-3 metabolism, Pluripotent Stem Cells cytology, SOXB1 Transcription Factors metabolism, Cell Cycle genetics, DNA Repair genetics, Gene Expression Regulation genetics, Pluripotent Stem Cells metabolism
- Abstract
Pluripotent stem cells are able to form any terminally differentiated cell. They have opened new doors for experimental and therapeutic studies to understand early development and to cure degenerative diseases in a way not previously possible. Nevertheless, it remains important to resolve and define the mechanisms underlying pluripotent stem cells, as that understanding will impact strongly on future medical applications. The capture of pluripotent stem cells in a dish is bound to several landmark discoveries, from the initial culture and phenotyping of pluripotent embryonal carcinoma cells to the recent induction of pluripotency in somatic cells. On this developmental time line, key transcription factors, such as Oct4, Sox2 or Nanog, have been revealed not only to regulate but also to functionally induce pluripotency. These early master regulators of development control developmental signalling pathways that affect the cell cycle, regulate gene expression, modulate the epigenetic state and repair DNA damage. Besides transcription factors, microRNAs have recently been shown to play important roles in gene expression and are embedded into the regulatory network orchestrating cellular development. However, there are species-specific differences in pluripotent cells, such as surface marker expression and growth factor requirements. Such differences and their underlying developmental pathways require clear definition and have major impacts on the preclinical test bed of pluripotent cells.
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- 2010
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50. High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity.
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Närvä E, Autio R, Rahkonen N, Kong L, Harrison N, Kitsberg D, Borghese L, Itskovitz-Eldor J, Rasool O, Dvorak P, Hovatta O, Otonkoski T, Tuuri T, Cui W, Brüstle O, Baker D, Maltby E, Moore HD, Benvenisty N, Andrews PW, Yli-Harja O, and Lahesmaa R
- Subjects
- Base Sequence, Cell Culture Techniques methods, Humans, Molecular Sequence Data, DNA genetics, DNA Copy Number Variations genetics, DNA Mutational Analysis methods, Embryonic Stem Cells classification, Embryonic Stem Cells physiology, Genetic Variation genetics, Sequence Analysis, DNA methods
- Abstract
Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected.
- Published
- 2010
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