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4 results on '"Apua C M, Paquola"'

1. Human archetypal pluripotent stem cells differentiate into trophoblast stem cells via endogenous BMP5/7 induction without transitioning through naive state

Author

Ethan Tietze, Andre Rocha Barbosa, Bruno Araujo, Veronica Euclydes, Bailey Spiegelberg, Hyeon Jin Cho, Yong Kyu Lee, Yanhong Wang, Alejandra McCord, Alan Lorenzetti, Arthur Feltrin, Joyce van de Leemput, Pasquale Di Carlo, Gianluca Ursini, Kynon J. Benjamin, Helena Brentani, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, Ronald McKay, Joo Heon Shin, Tomoyo Sawada, Apua C. M. Paquola, and Jennifer A. Erwin

Subjects
Medicine, Science
Abstract

Abstract Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGFβ), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)—a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.

Published
2024
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2. Variation in TAF1 Expression in Female Carrier-Induced Pluripotent Stem Cells and Human Brain Ontogeny Has Implications for Adult Neostriatum Vulnerability in X-Linked Dystonia Parkinsonism

Author

Laura D’Ignazio, Ricardo S. Jacomini, Bareera Qamar, Kynon J. M. Benjamin, Ria Arora, Tomoyo Sawada, Taylor A. Evans, Kenneth E. Diffenderfer, Aimee R. Pankonin, William T. Hendriks, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger, D. Cristopher Bragg, Apua C. M. Paquola, and Jennifer A. Erwin

Subjects
General Neuroscience, General Medicine
Abstract

X-linked dystonia-parkinsonism (XDP) is an inherited, X-linked, adult-onset movement disorder characterized by degeneration in the neostriatum. No therapeutics alter disease progression. The mechanisms underlying regional differences in degeneration and adult onset are unknown. Developing therapeutics requires a deeper understanding of how XDP-relevant features vary in health and disease. XDP is possibly due, in part, to a partial loss ofTAF1function. A disease-specific SINE-VNTR-Alu (SVA) retrotransposon insertion occurs within intron 32 ofTAF1, a subunit of TFIID involved in transcription initiation. While all XDP males are usually clinically affected, females are heterozygous carriers generally not manifesting the full syndrome. As a resource for disease modeling, we characterized eight iPSC lines from three XDP female carrier individuals for X chromosome inactivation (XCI) status and identified clonal lines that express either the wild-type X or XDP haplotype. Furthermore, we characterized XDP-relevant transcript expression in neurotypical humans, and found that SVA-F expression decreases after 30 years of age in the brain and thatTAF1is decreased in most female samples. Uniquely in the caudate nucleus,TAF1expression is not sexually dimorphic and decreased after adolescence. These findings indicate that regional-specific, age-specific, and sex-specific mechanisms regulateTAF1, highlighting the importance of disease-relevant models and postmortem tissue. We propose that the decreasedTAF1expression in the adult caudate may synergize with the XDP-specific partial loss ofTAF1function in patients, thereby passing a minimum threshold ofTAF1function, and triggering degeneration in the neostriatum.

Published
2022
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3. Cytoplasmic synthesis of endogenous

Author

Shinichi, Fukuda, Akhil, Varshney, Benjamin J, Fowler, Shao-Bin, Wang, Siddharth, Narendran, Kameshwari, Ambati, Tetsuhiro, Yasuma, Joseph, Magagnoli, Hannah, Leung, Shuichiro, Hirahara, Yosuke, Nagasaka, Reo, Yasuma, Ivana, Apicella, Felipe, Pereira, Ryan D, Makin, Eamonn, Magner, Xinan, Liu, Jian, Sun, Mo, Wang, Kirstie, Baker, Kenneth M, Marion, Xiwen, Huang, Elmira, Baghdasaryan, Meenakshi, Ambati, Vidya L, Ambati, Akshat, Pandey, Lekha, Pandya, Tammy, Cummings, Daipayan, Banerjee, Peirong, Huang, Praveen, Yerramothu, Genrich V, Tolstonog, Ulrike, Held, Jennifer A, Erwin, Apua C M, Paquola, Joseph R, Herdy, Yuichiro, Ogura, Hiroko, Terasaki, Tetsuro, Oshika, Shaban, Darwish, Ramendra K, Singh, Saghar, Mozaffari, Deepak, Bhattarai, Kyung Bo, Kim, James W, Hardin, Charles L, Bennett, David R, Hinton, Timothy E, Hanson, Christian, Röver, Keykavous, Parang, Nagaraj, Kerur, Jinze, Liu, Brian C, Werner, S Scott, Sutton, Srinivas R, Sadda, Gerald G, Schumann, Bradley D, Gelfand, Fred H, Gage, and Jayakrishna, Ambati

Subjects
endocrine system, Cytoplasm, DNA, Complementary, Retroelements, Reverse Transcription, Biological Sciences, Epithelium, Macular Degeneration, Long Interspersed Nucleotide Elements, Alu Elements, hemic and lymphatic diseases, Animals, Humans, Retinal Pigments
Abstract

Alu retroelements propagate via retrotransposition by hijacking long interspersed nuclear element-1 (L1) reverse transcriptase (RT) and endonuclease activities. Reverse transcription of Alu RNA into complementary DNA (cDNA) is presumed to occur exclusively in the nucleus at the genomic integration site. Whether Alu cDNA is synthesized independently of genomic integration is unknown. Alu RNA promotes retinal pigmented epithelium (RPE) death in geographic atrophy, an untreatable type of age-related macular degeneration. We report that Alu RNA-induced RPE degeneration is mediated via cytoplasmic L1–reverse-transcribed Alu cDNA independently of retrotransposition. Alu RNA did not induce cDNA production or RPE degeneration in L1-inhibited animals or human cells. Alu reverse transcription can be initiated in the cytoplasm via self-priming of Alu RNA. In four health insurance databases, use of nucleoside RT inhibitors was associated with reduced risk of developing atrophic macular degeneration (pooled adjusted hazard ratio, 0.616; 95% confidence interval, 0.493–0.770), thus identifying inhibitors of this Alu replication cycle shunt as potential therapies for a major cause of blindness.

Published
2021

4. The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

Author

Helena, Brentani, Otávia L, Caballero, Anamaria A, Camargo, Aline M, da Silva, Wilson Araújo, da Silva, Emmanuel, Dias Neto, Marco, Grivet, Arthur, Gruber, Pedro Edson Moreira, Guimaraes, Winston, Hide, Christian, Iseli, C Victor, Jongeneel, Janet, Kelso, Maria Aparecida, Nagai, Elida Paula Benquique, Ojopi, Elisson C, Osorio, Eduardo M R, Reis, Gregory J, Riggins, Andrew John George, Simpson, Sandro, de Souza, Brian J, Stevenson, Robert L, Strausberg, Eloiza H, Tajara, Sergio, Verjovski-Almeida, Marcio Luis, Acencio, Mário Henrique, Bengtson, Fabiana, Bettoni, Walter F, Bodmer, Marcelo R S, Briones, Luiz Paulo, Camargo, Webster, Cavenee, Janete M, Cerutti, Luis Eduardo, Coelho Andrade, Paulo César, Costa dos Santos, Maria Cristina, Ramos Costa, Israel Tojal, da Silva, Marcos Roberto H, Estécio, Karine, Sa Ferreira, Frank B, Furnari, Milton, Faria, Pedro A F, Galante, Gustavo S, Guimaraes, Adriano Jesus, Holanda, Edna Teruko, Kimura, Maarten R, Leerkes, Xin, Lu, Rui M B, Maciel, Elizabeth A L, Martins, Katlin Brauer, Massirer, Analy S A, Melo, Carlos Alberto, Mestriner, Elisabete Cristina, Miracca, Leandro Lorenco, Miranda, Francisco G, Nobrega, Paulo S, Oliveira, Apua C M, Paquola, José Rodrigo C, Pandolfi, Maria Ines de Moura, Campos Pardini, Fabio, Passetti, John, Quackenbush, Beatriz, Schnabel, Mari Cleide, Sogayar, Jorge E, Souza, Sandro R, Valentini, Andre C, Zaiats, Elisabete Jorge, Amaral, Liliane A T, Arnaldi, Amelia Goes, de Araújo, Simone Aparecida, de Bessa, David C, Bicknell, Maria Eugenia, Ribeiro de Camaro, Dirce Maria, Carraro, Helaine, Carrer, Alex F, Carvalho, Christian, Colin, Fernando, Costa, Cyntia, Curcio, Ismael Dale Cotrim, Guerreiro da Silva, Neusa, Pereira da Silva, Márcia, Dellamano, Hamza, El-Dorry, Enilza Maria, Espreafico, Ari José, Scattone Ferreira, Cristiane, Ayres Ferreira, Maria Angela H Z, Fortes, Angelita Habr, Gama, Daniel, Giannella-Neto, Maria Lúcia C C, Giannella, Ricardo R, Giorgi, Gustavo Henrique, Goldman, Maria Helena S, Goldman, Christine, Hackel, Paulo Lee, Ho, Elza Myiuki, Kimura, Luiz Paulo, Kowalski, Jose E, Krieger, Luciana C C, Leite, Ademar, Lopes, Ana Mercedes S C, Luna, Alan, Mackay, Suely Kazue Nagahashi, Mari, Adriana Aparecida, Marques, Waleska K, Martins, André, Montagnini, Mario, Mourão Neto, Ana Lucia T O, Nascimento, A Munro, Neville, Marina P, Nobrega, Mike J, O'Hare, Audrey Yumi, Otsuka, Anna Izabel, Ruas de Melo, Maria Luisa, Paco-Larson, Gonçalo, Guimarães Pereira, Joao Bosco, Pesquero, Juliana Gilbert, Pessoa, Paula, Rahal, Claudia Aparecida, Rainho, Vanderlei, Rodrigues, Silvia Regina, Rogatto, Camila Malta, Romano, Janaina Gusmao, Romeiro, Benedito Mauro, Rossi, Monica, Rusticci, Renata, Guerra de Sá, Simone Cristina, Sant' Anna, Miriam L, Sarmazo, Teresa Cristina de Lima E, Silva, Fernando Augusto, Soares, Maria de Fátima, Sonati, Josane, de Freitas Sousa, Diana, Queiroz, Valéria, Valente, André Luiz, Vettore, Fabiola Elizabeth, Villanova, Marco Antonio, Zago, and Heloisa, Zalcberg

Subjects
Nonsynonymous substitution, Genetics, Expressed Sequence Tags, Expressed sequence tag, Multidisciplinary, Proteome, Chromosome Mapping, Genetic Variation, Computational biology, Biology, Biological Sciences, Genome, Polymorphism, Single Nucleotide, DNA sequencing, Transcriptome, Gene Expression Regulation, Neoplastic, Neoplasms, Databases, Genetic, Humans, Human genome, Tissue Distribution, RNA, Messenger, Gene
Abstract

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define ≈23,500 genes, of which only ≈1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that

Published
2003

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