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2,569 results on '"NAKAMURA, Yukio"'

9. Understanding the Relationship Between Adverse Medication Use and Falls Among Older Patients Receiving Home Medical Care: OHCARE study.

Author

Murakami, Naoko, Kabayama, Mai, Yano, Tomoko, Nakamura, Chika, Fukata, Yuka, Morioka, Chihiro, Fang, Wen, Nako, Yumiko, Omichi, Yuki, Koujiya, Eriko, Godai, Kayo, Kido, Michiko, Tseng, Winston, Nakamura, Toshinori, Hirotani, Atsushi, Fukuda, Toshio, Tamatani, Michio, Okuda, Yoshinari, Ikushima, Masashi, Baba, Yoshichika, Nagano, Masahiro, Nakamura, Yukio, Rakugi, Hiromi, and Kamide, Kei

Subjects
falls, home medical care, older patients, polypharmacy
Abstract

Objective: Previous studies suggest older patients with multiple health conditions and medications may experience adverse interactions, leading to negative outcomes. However, theres limited research on this in older adults receiving home medical care. This study assesses whether polypharmacy is linked to falls or other clinical outcomes. Methods: The study population included 217 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan. The survey examined the association between polypharmacy and clinical outcomes. We defined polypharmacy as six or more medications taken regularly. Results: Of the participants, 135 (62.6%) had polypharmacy and were significantly more likely to have hypertension or diabetes. Common medications included those for hypertension, diabetes, and mental disorders. Participants with polypharmacy experienced significantly more falls. Multivariate analysis showed an association between polypharmacy and falls (odds ratio: 2.81, 95% confidence interval [1.34, 5.92]). Conclusion: Even in older patients receiving home health care, the use of six or more medications poses a risk of falls. Careful observations and life support by medical stuffs are necessary to prevent falls in older patients with polypharmacy receiving home medical care.

Published
2024

15. Precise correction of a spectrum of β-thalassemia mutations in coding and non-coding regions by base editors

Author

Prasad, Kirti, Devaraju, Nivedhitha, George, Anila, Ravi, Nithin Sam, Paul, Joshua, Mahalingam, Gokulnath, Rajendiran, Vignesh, Panigrahi, Lokesh, Venkatesan, Vigneshwaran, Lakhotiya, Kartik, Periyasami, Yogapriya, Pai, Aswin Anand, Nakamura, Yukio, Kurita, Ryo, Balasubramanian, Poonkuzhali, Thangavel, Saravanabhavan, Velayudhan, Shaji R., Newby, Gregory A., Marepally, Srujan, Srivastava, Alok, and Mohankumar, Kumarasamypet M.

Published
2024
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16. Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin

Author

Ravi, Nithin Sam, Wienert, Beeke, Wyman, Stacia K, Bell, Henry William, George, Anila, Mahalingam, Gokulnath, Vu, Jonathan T, Prasad, Kirti, Bandlamudi, Bhanu Prasad, Devaraju, Nivedhitha, Rajendiran, Vignesh, Syedbasha, Nazar, Pai, Aswin Anand, Nakamura, Yukio, Kurita, Ryo, Narayanasamy, Muthuraman, Balasubramanian, Poonkuzhali, Thangavel, Saravanabhavan, Marepally, Srujan, Velayudhan, Shaji R, Srivastava, Alok, DeWitt, Mark A, Crossley, Merlin, Corn, Jacob E, and Mohankumar, Kumarasamypet M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Hematology, Rare Diseases, Sickle Cell Disease, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adenine, Anemia, Sickle Cell, CRISPR-Cas Systems, Cell Line, Clustered Regularly Interspaced Short Palindromic Repeats, Cytosine, Fetal Hemoglobin, Gene Editing, Hematopoietic Stem Cells, Humans, Point Mutation, Promoter Regions, Genetic, beta-Globins, beta-Thalassemia, gamma-Globins, base editing, globin regulation, HPFH mutations, beta-hemoglobinopathies, fetal hemoglobin, CRISPR, Cas9, Base editing, Beta hemoglobinopathies, Fetal hemoglobin, Globin regulation, HBGpromoter, Sickle cell disease, Beta-thalassemia, Large deletions, CD34+HSPCs, CRISPR/Cas9, beta hemoglobinopathies, beta-thalassemia, cd34+ hspcs, chromosomes, crispr/cas9, gene expression, genetics, genomics, hbgpromoter, hpfh mutations, large deletions, sickle cell disease, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Naturally occurring point mutations in the HBG promoter switch hemoglobin synthesis from defective adult beta-globin to fetal gamma-globin in sickle cell patients with hereditary persistence of fetal hemoglobin (HPFH) and ameliorate the clinical severity. Inspired by this natural phenomenon, we tiled the highly homologous HBG proximal promoters using adenine and cytosine base editors that avoid the generation of large deletions and identified novel regulatory regions including a cluster at the -123 region. Base editing at -123 and -124 bp of HBG promoter induced fetal hemoglobin (HbF) to a higher level than disruption of well-known BCL11A binding site in erythroblasts derived from human CD34+ hematopoietic stem and progenitor cells (HSPC). We further demonstrated in vitro that the introduction of -123T > C and -124T > C HPFH-like mutations drives gamma-globin expression by creating a de novo binding site for KLF1. Overall, our findings shed light on so far unknown regulatory elements within the HBG promoter and identified additional targets for therapeutic upregulation of fetal hemoglobin.

Published
2022

18. Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression

Author

Rajendiran, Vignesh, Devaraju, Nivedhitha, Haddad, Mahdi, Ravi, Nithin Sam, Panigrahi, Lokesh, Paul, Joshua, Gopalakrishnan, Chandrasekar, Wyman, Stacia, Ariudainambi, Keerthiga, Mahalingam, Gokulnath, Periyasami, Yogapriya, Prasad, Kirti, George, Anila, Sukumaran, Dhiyaneshwaran, Gopinathan, Sandhiya, Pai, Aswin Anand, Nakamura, Yukio, Balasubramanian, Poonkuzhali, Ramalingam, Rajasekaran, Thangavel, Saravanabhavan, Velayudhan, Shaji R., Corn, Jacob E., Mackay, Joel P., Marepally, Srujan, Srivastava, Alok, Crossley, Merlin, and Mohankumar, Kumarasamypet M.

Published
2024
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19. Pre-existing cross-reactive neutralizing activity against SARS-CoV-2 and seasonal coronaviruses prior to the COVID-19 pandemic (2014-2019) with limited immunity against recent emerging SARS-CoV-2 variants, Vietnam

Author

Nguyen, Thi Thanh Ngan, Choo, Ee Mei, Nakamura, Yukio, Suzuki, Ryuji, Shiina, Takashi, Shin-I, Tadasu, Fukuta, Mizuki, Nguyen, Co Thach, Nguyen, Thi Thu Thuy, Nguyen, Le Khanh Hang, Hoang, Vu Mai Phuong, Morita, Kouichi, Dang, Duc Anh, Hasebe, Futoshi, Le, Thi Quynh Mai, and Moi, Meng Ling

Published
2024
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20. Mobile element variation contributes to population-specific genome diversification, gene regulation and disease risk

Author

Kojima, Shohei, Koyama, Satoshi, Ka, Mirei, Saito, Yuka, Parrish, Erica H., Endo, Mikiko, Takata, Sadaaki, Mizukoshi, Misaki, Hikino, Keiko, Takeda, Atsushi, Gelinas, Asami F., Heaton, Steven M., Koide, Rie, Kamada, Anselmo J., Noguchi, Michiya, Hamada, Michiaki, Kamatani, Yoichiro, Murakawa, Yasuhiro, Ishigaki, Kazuyoshi, Nakamura, Yukio, Ito, Kaoru, Terao, Chikashi, Momozawa, Yukihide, and Parrish, Nicholas F.

Published
2023
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22. A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression

Author

Takase, Shohei, Hiroyama, Takashi, Shirai, Fumiyuki, Maemoto, Yuki, Nakata, Akiko, Arata, Mayumi, Matsuoka, Seiji, Sonoda, Takeshi, Niwa, Hideaki, Sato, Shin, Umehara, Takashi, Shirouzu, Mikako, Nishigaya, Yosuke, Sumiya, Tatsunobu, Hashimoto, Noriaki, Namie, Ryosuke, Usui, Masaya, Ohishi, Tomokazu, Ohba, Shun-ichi, Kawada, Manabu, Hayashi, Yoshihiro, Harada, Hironori, Yamaguchi, Tokio, Shinkai, Yoichi, Nakamura, Yukio, Yoshida, Minoru, and Ito, Akihiro

Published
2023
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24. Chemically defined cytokine-free expansion of human haematopoietic stem cells

Author

Sakurai, Masatoshi, Ishitsuka, Kantaro, Ito, Ryoji, Wilkinson, Adam C., Kimura, Takaharu, Mizutani, Eiji, Nishikii, Hidekazu, Sudo, Kazuhiro, Becker, Hans Jiro, Takemoto, Hiroshi, Sano, Tsubasa, Kataoka, Keisuke, Takahashi, Satoshi, Nakamura, Yukio, Kent, David G., Iwama, Atsushi, Chiba, Shigeru, Okamoto, Shinichiro, Nakauchi, Hiromitsu, and Yamazaki, Satoshi

Published
2023
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27. Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development.

Author

Afouda, Boni A, Nakamura, Yukio, Shaw, Sophie, Charney, Rebekah M, Paraiso, Kitt D, Blitz, Ira L, Cho, Ken WY, and Hoppler, Stefan

Subjects
Biological Sciences, Developmental Biology, Molecular Biology
Abstract

Although Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target gene expression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target gene regulation. We combine transcriptomics using RNA-seq with genome-wide β-catenin association using ChIP-seq to identify stage-specific direct Wnt target genes. We propose coherent feedforward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin association overlaps with Foxh1-associated regulatory sequences and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease.

Published
2020

28. Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Author

Morgan, Richard A, Ma, Feiyang, Unti, Mildred J, Brown, Devin, Ayoub, Paul George, Tam, Curtis, Lathrop, Lindsay, Aleshe, Bamidele, Kurita, Ryo, Nakamura, Yukio, Senadheera, Shantha, Wong, Ryan L, Hollis, Roger P, Pellegrini, Matteo, and Kohn, Donald B

Subjects
ChromHMM, Functional dissection, MPRA, Massively Parrallel Reporter Assay, SCD, STARR-seq, Shuffling, hemoglobin, rational lentiviral vector design, sickle cell disease
Abstract

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

Published
2020

29. Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies

Author

Venkatesan, Vigneshwaran, Christopher, Abisha Crystal, Rhiel, Manuel, Azhagiri, Manoj Kumar K., Babu, Prathibha, Walavalkar, Kaivalya, Saravanan, Bharath, Andrieux, Geoffroy, Rangaraj, Sumathi, Srinivasan, Saranya, Karuppusamy, Karthik V., Jacob, Annlin, Bagchi, Abhirup, Pai, Aswin Anand, Nakamura, Yukio, Kurita, Ryo, Balasubramanian, Poonkuzhali, Pai, Rekha, Marepally, Srujan Kumar, Mohankumar, Kumarasamypet Murugesan, Velayudhan, Shaji R., Boerries, Melanie, Notani, Dimple, Cathomen, Toni, Srivastava, Alok, and Thangavel, Saravanabhavan

Published
2023
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32. HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation

Author

Dulmovits, Brian M., Tang, Yuefeng, Papoin, Julien, He, Mingzhu, Li, Jianhua, Yang, Huan, Addorisio, Meghan E., Kennedy, Lauren, Khan, Mushran, Brindley, Elena, Ashley, Ryan J., Ackert-Bicknell, Cheryl, Hale, John, Kurita, Ryo, Nakamura, Yukio, Diamond, Betty, Barnes, Betsy J., Hermine, Olivier, Gallagher, Patrick G., Steiner, Laurie A., Lipton, Jeffrey M., Taylor, Naomi, Mohandas, Narla, Andersson, Ulf, Al-Abed, Yousef, Tracey, Kevin J., and Blanc, Lionel

Published
2022
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33. Therapy with transitions from one bone-forming agent to another: a retrospective cohort study on teriparatide and romosozumab.

Author

Kobayakawa, Tomonori, Kanayama, Yasuhide, Hirano, Yuji, Yukishima, Toshitaka, and Nakamura, Yukio

Subjects
BONE density, BONE remodeling, TERIPARATIDE, AGE groups, COHORT analysis, LUMBAR vertebrae, FEMUR neck
Abstract

This study aimed to evaluate the effectiveness of sequential therapy with a bone formation-promoting agent (either teriparatide or romosozumab) for osteoporosis treatment following prior treatment with the other bone-forming agent (teriparatide or romosozumab). This is a multicenter retrospective cohort study observing 2 groups for comparison: one with 69 patients transitioning from teriparatide to romosozumab (the T2R group) and the other with 25 patients transitioning from romosozumab to teriparatide (the R2T group), monitored for 12 months on the second drug. Key outcomes included changes in bone mineral density (BMD), bone turnover marker changes, and adverse events. The mean ages of each group were 72.3 years in the T2R group and 67.6 years in the R2T group, with the proportions of women being 91.3% and 80.0%, respectively. The percent changes of BMD in the lumbar spine after 12 months of sequential therapy were +10.8% in the T2R group (p  < .001 versus baseline) and −0.0% in the R2T group (p  = .875). The percent changes in BMD in the total hip and femoral neck were +4.4% and +4.4% in the T2R group, and −1.3% and −0.8% in the R2T group, respectively. When comparing the 2 groups, BMD changes at all sites in the T2R group were significantly higher than those in the R2T group (p  < .001). Furthermore, when examining the changes in the proportion of patients who achieved the osteoporosis treatment goal of a T-score exceeding −2.5, no significant increase was observed in the R2T group, whereas a significant increase was observed in the lumbar spine in the T2R group. Regarding therapy switching between bone-forming agents, this study suggests that transitioning from teriparatide to romosozumab increases BMD more effectively than transitioning in the opposite sequence. [ABSTRACT FROM AUTHOR]

Published
2024
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37. CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells

Author

Chung, Jennifer E, Magis, Wendy, Vu, Jonathan, Heo, Seok-Jin, Wartiovaara, Kirmo, Walters, Mark C, Kurita, Ryo, Nakamura, Yukio, Boffelli, Dario, Martin, David I. K, Corn, Jacob E, and DeWitt, Mark A

Subjects
BRII recipient: DeWitt
Abstract

Sickle Cell Disease and ß-thalassemia, which are caused by defective or deficient adult ß-globin (HBB) respectively, are the most common serious genetic blood diseases in the world. Persistent expression of the fetal ß-like globin, also known as ?-globin, can ameliorate both disorders by serving in place of the adult ß-globin as a part of the fetal hemoglobin tetramer (HbF). Here we use CRISPR-Cas9 gene editing to explore a potential ?-globin silencer region upstream of the δ-globin gene identified by comparison of naturally-occurring deletion mutations associated with up-regulated ?-globin. We find that deletion of a 1.7 kb consensus element or select 350 bp sub-regions from bulk populations of cells increases levels of HbF. Screening of individual sgRNAs in one sub-region revealed three single guides that caused increases in ?-globin expression. Deletion of the 1.7 kb region in HUDEP-2 clonal sublines, and in colonies derived from CD34+ hematopoietic stem/progenitor cells (HSPCs), does not cause significant up-regulation of ?-globin. These data suggest that the 1.7 kb region is not an autonomous ?-globin silencer, and thus by itself is not a suitable therapeutic target for gene editing treatment of ß-hemoglobinopathies.

Published
2019

44. Generation of human induced pluripotent stem cell lines derived from four Rett syndrome patients with MECP2 mutations

Author

Mori, Miyu, primary, Yoshii, Shoko, additional, Noguchi, Michiya, additional, Takagi, Daigo, additional, Shimizu, Tomoya, additional, Ito, Hidenori, additional, Matsuo-Takasaki, Mami, additional, Nakamura, Yukio, additional, Takahashi, Satoru, additional, Hamada, Hiromichi, additional, Ohnuma, Kiyoshi, additional, Shiohama, Tadashi, additional, and Hayashi, Yohei, additional

Published
2024
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45. Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

Author

Daniels, Deborah E., Ferguson, Daniel C.J., Griffiths, Rebecca E., Trakarnsanga, Kongtana, Cogan, Nicola, MacInnes, Katherine A., Mordue, Kathryn E., Andrienko, Tatyana, Ferrer-Vicens, Ivan, Ramos Jiménez, Daniel, Lewis, Phillip A., Wilson, Marieangela C., Canham, Maurice A., Kurita, Ryo, Nakamura, Yukio, Anstee, David J., and Frayne, Jan

Published
2021
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48. Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos.

Author

Hodonsky, Chani J, Jain, Deepti, Schick, Ursula M, Morrison, Jean V, Brown, Lisa, McHugh, Caitlin P, Schurmann, Claudia, Chen, Diane D, Liu, Yong Mei, Auer, Paul L, Laurie, Cecilia A, Taylor, Kent D, Browning, Brian L, Li, Yun, Papanicolaou, George, Rotter, Jerome I, Kurita, Ryo, Nakamura, Yukio, Browning, Sharon R, Loos, Ruth JF, North, Kari E, Laurie, Cathy C, Thornton, Timothy A, Pankratz, Nathan, Bauer, Daniel E, Sofer, Tamar, and Reiner, Alex P

Subjects
Erythrocytes, Humans, Proteasome Endopeptidase Complex, Hemoglobins, Homeodomain Proteins, Tumor Suppressor Proteins, Erythrocyte Count, Polymorphism, Single Nucleotide, Hispanic Americans, Female, Male, Genome-Wide Association Study, alpha-Globins, beta-Globins, RNA, Long Noncoding, Solute Carrier Family 12, Member 2, Polymorphism, Single Nucleotide, RNA, Long Noncoding, Solute Carrier Family 12, Member 2, Genetics, Developmental Biology
Abstract

Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos.

Published
2017

49. An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors

Author

Ieyasu, Aki, Ishida, Reiko, Kimura, Takaharu, Morita, Maiko, Wilkinson, Adam C, Sudo, Kazuhiro, Nishimura, Toshinobu, Ohehara, Jun, Tajima, Yoko, Lai, Chen-Yi, Otsu, Makoto, Nakamura, Yukio, Ema, Hideo, Nakauchi, Hiromitsu, and Yamazaki, Satoshi

Subjects
Stem Cell Research - Nonembryonic - Non-Human, Transplantation, Biotechnology, Stem Cell Research, Hematology, Regenerative Medicine, Development of treatments and therapeutic interventions, 1.1 Normal biological development and functioning, Underpinning research, 5.2 Cellular and gene therapies, Blood, Animals, Blood Proteins, Cell Culture Techniques, Cell Differentiation, Cell Proliferation, Cell Self Renewal, Colony-Forming Units Assay, Hematopoietic Stem Cells, Hemopexin, Interleukin-1alpha, Mice, Recombinant Proteins, BSA, FCS, all-recombinant protein-based culture system, hematopoietic stem cell, hemopexin, Biochemistry and Cell Biology, Clinical Sciences
Abstract

Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations.

Published
2017

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