Alteration of differentiation potentials by modulating GATA transcription factors in murine embryonic stem cells

Xiangxi Xu, Callinice D. Capo-Chichi, Jennifer L. Smedberg, Malgorzata Rula, Emmanuelle Nicolas, Anthony T. Yeung, Richard F. Adamo, Andrey Frolov, Andrew K. Godwin

Research output: Contribution to journalArticle

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Abstract

Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (-/-) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (-/-) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (-/-) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy.

Original languageEnglish
Article number602068
JournalStem Cells International
DOIs
StatePublished - Dec 1 2010

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GATA Transcription Factors
Endoderm
Embryonic Stem Cells
Mesoderm
Tretinoin
Hepatocyte Nuclear Factor 4
alpha-Fetoproteins
Laminin
Cell- and Tissue-Based Therapy
Cardiac Myocytes
Cell Differentiation
Collagen
Gene Expression
Liver

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Alteration of differentiation potentials by modulating GATA transcription factors in murine embryonic stem cells. / Xu, Xiangxi; Capo-Chichi, Callinice D.; Smedberg, Jennifer L.; Rula, Malgorzata; Nicolas, Emmanuelle; Yeung, Anthony T.; Adamo, Richard F.; Frolov, Andrey; Godwin, Andrew K.

In: Stem Cells International, 01.12.2010.

Research output: Contribution to journalArticle

Xu, Xiangxi ; Capo-Chichi, Callinice D. ; Smedberg, Jennifer L. ; Rula, Malgorzata ; Nicolas, Emmanuelle ; Yeung, Anthony T. ; Adamo, Richard F. ; Frolov, Andrey ; Godwin, Andrew K. / Alteration of differentiation potentials by modulating GATA transcription factors in murine embryonic stem cells. In: Stem Cells International. 2010.
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abstract = "Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (-/-) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (-/-) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (-/-) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy.",
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AU - Capo-Chichi, Callinice D.

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AU - Rula, Malgorzata

AU - Nicolas, Emmanuelle

AU - Yeung, Anthony T.

AU - Adamo, Richard F.

AU - Frolov, Andrey

AU - Godwin, Andrew K.

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