MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation

Hsiao-Ning Huang, Shao Yin Chen, Shiaw Min Hwang, Ching Chia Yu, Ming Wei Su, Wei Mai, Hsei Wei Wang, Wei Chung Cheng, Scott C. Schuyler, Nianhan Ma, Frank Leigh Lu, Jean Lu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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[U+F029])/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.

Original languageEnglish
Pages (from-to)338-353
Number of pages16
JournalStem Cell Research
Volume12
Issue number2
DOIs
Publication statusPublished - 2014 Mar 1

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Cell Differentiation
Carrier Proteins
Embryoid Bodies
Down-Regulation
Endoderm
Ectoderm
Mesoderm
Apoptosis
Feeder Cells
Human Embryonic Stem Cells
Cell Self Renewal
Fibroblast Growth Factors
Transforming Growth Factors
3' Untranslated Regions

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

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. / MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation. In: Stem Cell Research. 2014 ; Vol. 12, No. 2. pp. 338-353.
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abstract = "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[U+F029])/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.",
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Huang, H-N, Chen, SY, Hwang, SM, Yu, CC, Su, MW, Mai, W, Wang, HW, Cheng, WC, Schuyler, SC, Ma, N, Lu, FL & Lu, J 2014, 'MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation', Stem Cell Research, vol. 12, no. 2, pp. 338-353. https://doi.org/10.1016/j.scr.2013.11.009

MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation. / 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.

In: Stem Cell Research, Vol. 12, No. 2, 01.03.2014, p. 338-353.

Research output: Contribution to journalArticle

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T1 - MiR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation

AU - Huang, Hsiao-Ning

AU - Chen, Shao Yin

AU - Hwang, Shiaw Min

AU - Yu, Ching Chia

AU - Su, Ming Wei

AU - Mai, Wei

AU - Wang, Hsei Wei

AU - Cheng, Wei Chung

AU - Schuyler, Scott C.

AU - Ma, Nianhan

AU - Lu, Frank Leigh

AU - Lu, Jean

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AB - 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[U+F029])/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.

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