Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Callinice D. Capo-chichi, Jennifer L. Smedberg, Malgorzata Rula, Emmanuelle Nicolas, Anthony T. Yeung, Richard F. Adamo, Andrey Frolov, Andrew K. Godwin, Xiang-Xi Xu
Format: Article
Language:English
Published: Wiley 2010-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.4061/2010/602068
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832561732583686144
author Callinice D. Capo-chichi
Jennifer L. Smedberg
Malgorzata Rula
Emmanuelle Nicolas
Anthony T. Yeung
Richard F. Adamo
Andrey Frolov
Andrew K. Godwin
Xiang-Xi Xu
author_facet Callinice D. Capo-chichi
Jennifer L. Smedberg
Malgorzata Rula
Emmanuelle Nicolas
Anthony T. Yeung
Richard F. Adamo
Andrey Frolov
Andrew K. Godwin
Xiang-Xi Xu
author_sort Callinice D. Capo-chichi
collection DOAJ
description 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.
format Article
id doaj-art-cbc9c369783b4dd0a0a6dc3ff37394f7
institution Kabale University
issn 1687-9678
language English
publishDate 2010-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-cbc9c369783b4dd0a0a6dc3ff37394f72025-02-03T01:24:24ZengWileyStem Cells International1687-96782010-01-01201010.4061/2010/602068602068Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem CellsCallinice D. Capo-chichi0Jennifer L. Smedberg1Malgorzata Rula2Emmanuelle Nicolas3Anthony T. Yeung4Richard F. Adamo5Andrey Frolov6Andrew K. Godwin7Xiang-Xi Xu8Miller School of Medicine, University of Miami, 1550 NW 10th Avenue (M877), Miami, FL 33156, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USAMiller School of Medicine, University of Miami, 1550 NW 10th Avenue (M877), Miami, FL 33156, USABackground. 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.http://dx.doi.org/10.4061/2010/602068
spellingShingle Callinice D. Capo-chichi
Jennifer L. Smedberg
Malgorzata Rula
Emmanuelle Nicolas
Anthony T. Yeung
Richard F. Adamo
Andrey Frolov
Andrew K. Godwin
Xiang-Xi Xu
Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
Stem Cells International
title Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
title_full Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
title_fullStr Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
title_full_unstemmed Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
title_short Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
title_sort alteration of differentiation potentials by modulating gata transcription factors in murine embryonic stem cells
url http://dx.doi.org/10.4061/2010/602068
work_keys_str_mv AT callinicedcapochichi alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT jenniferlsmedberg alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT malgorzatarula alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT emmanuellenicolas alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT anthonytyeung alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT richardfadamo alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT andreyfrolov alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT andrewkgodwin alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells
AT xiangxixu alterationofdifferentiationpotentialsbymodulatinggatatranscriptionfactorsinmurineembryonicstemcells