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| 題名: | MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation |
| 作者: | 馬念涵;Huang, Hsiao-Ning;Chen, Shao-Yin;Hwang, Shiaw-Min;Yu, Ching-Chia;Su, Ming-Wei;Mai, Wei;Wang, Hsei-Wei;Cheng, Wei-Chung;Schuyler, Scott C.;Ma, Nianhan;Lu, Frank Leigh;Lu, Jean |
| 貢獻者: | 生醫理工學院生醫科學與工程學系 |
| 關鍵詞: | Activins - metabolism;Apoptosis - physiology;Cell Differentiation - physiology;Cell Line;Cell Lineage;Down-Regulation;Embryonic Stem Cells - cytology;Embryonic Stem Cells - metabolism;GATA4 Transcription Factor - genetics;GATA4 Transcription Factor - metabolism;GATA4 Transcription Factor - physiology;Gene Knockdown Techniques;HEK293 Cells;Humans;MicroRNAs - genetics;MicroRNAs - metabolism;MicroRNAs - physiology;Signal Transduction;Transforming Growth Factor beta - metabolism |
| 日期: | 2014-03-01 |
| 上傳時間: | 2026-04-23 11:17:17 (UTC+8) |
| 出版者: | Elsevier;England: Elsevier B.V |
| 摘要: | 摘要： Human embryonic stem cells (hESCs) are functionally unique for their self-renewal ability and pluripotency, but the molecular mechanisms giving rise to these properties are not fully understood. hESCs can differentiate into embryoid bodies (EBs) containing ectoderm, mesoderm, and endoderm. In the miR-200 family, miR-200c was especially enriched in undifferentiated hESCs and significantly downregulated in EBs. The knockdown of the miR-200c in hESCs downregulated Nanog expression, upregulated GATA binding protein 4 (GATA4) expression, and induced hESC apoptosis. The knockdown of GATA4 rescued hESC apoptosis induced by downregulation of miR-200c. miR-200c directly targeted the 3′-untranslated region of GATA4. Interestingly, the downregulation of GATA4 significantly inhibited EB formation in hESCs. Overexpression of miR-200c inhibited EB formation and repressed the expression of ectoderm, endoderm, and mesoderm markers, which could partially be rescued by ectopic expression of GATA4. Fibroblast growth factor (FGF) and activin A/nodal can sustain hESC renewal in the absence of feeder layer. Inhibition of transforming growth factor-β (TGF-β)/activin A/nodal signaling by SB431542 treatment downregulated the expression of miR-200c. Overexpression of miR-200c partially rescued the expression of Nanog/phospho-Smad2 that was downregulated by SB431542 treatment. Our observations have uncovered novel functions of miR-200c and GATA4 in regulating hESC renewal and differentiation. [Display omitted] •miR-200c is essential for Nanog expression/hESC renewal, and blocks EB formation.•miR-200c directly targets GATA4 3′UTR and inhibits GATA4 expression.•Downregulation of GATA4 partially restores hESC renewal upon miR-200c knockdown.•Overexpression of GATA4 rescues EB formation and three lineages differentiation.•miR-200c and activin A/Smad pathway can regulate each other's expression/function.
其他題名： Stem Cell Res
出版者： England: Elsevier B.V
出版日期： 2014-03-01
出處： Stem cell research, 2014-03, Vol.12 (2), p.338-353
資源來源： Directory of Open Access Journals (DOAJ)
版權： 2013 The Authors
版權： Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
識別號： ISSN: 1873-5061
識別號： ISSN: 1876-7753
識別號： EISSN: 1876-7753
識別號： DOI: 10.1016/j.scr.2013.11.009
識別號： PMID: 24365599 |
| 顯示於類別: | [生醫科學與工程學系] 期刊論文
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