DOI: 10.1101/gad.968802. Differentiation of embryonic stem cells is induced by GATA factors

Differentiation of embryonic stem cells is induced by GATA factors

10.1101/gad.968802

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Extraembryonic endoderm (ExE) is differentiated from the inner cell mass of the late blastocyst-stage embryo to form visceral and parietal endoderm, both of which have an important role in early embryogenesis. The essential roles of Gata-6 and Gata-4 on differentiation of visceral endoderm have been identified by analyses of knockout mice. Here we report that forced expression of either Gata-6 or Gata-4 in embryonic stem (ES) cells is sufficient to induce the proper differentiation program towards ExE. We believe that this is the first report of a physiological differentiation event induced by the ectopic expression of a transcription factor in ES cells.

Bibliography

Fujikura, J., Yamato, E., Yonemura, S., Hosoda, K., Masui, S., Nakao, K., Miyazaki, J., & Niwa, H. (2002). Differentiation of embryonic stem cells is induced by GATA factors. Genes & Development, 16(7), 784â789.

Authors 8

Junji Fujikura (first)
Eiji Yamato (additional)
Shigenobu Yonemura (additional)
Kiminori Hosoda (additional)
Shinji Masui (additional)
Kazuwa Nakao (additional)
Jun-ichi Miyazaki (additional)
Hitoshi Niwa (additional)

References 37 Referenced 444

10.1006/excr.1996.0340
10.1242/dev.126.21.4795 / Development / Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification. by Barbacci (1999)
10.1073/pnas.84.3.709
10.1128/MCB.15.2.1034 / Mol. Cell. Biol. / A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. by Ben-Shushan (1995)
10.1128/MCB.18.4.1866 / Mol. Cell. Biol. / Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site. by Ben-Shushan (1998)
10.1242/dev.126.21.4785 / Development / Essential role for the homeoprotein vHNF1/HNF1beta in visceral endoderm differentiation. by Coffinier (1999)
10.1242/dev.126.3.535 / Development / BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. by Coucouvanis (1999)
10.1242/dev.124.2.279 / Development / Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: Tetraploid rescue of Hnf-4−/−. embryos. by Duncan (1997)
10.1126/science.281.5377.692
{'key': '2021111508034562000_16.7.784.10', 'first-page': '289', 'article-title': 'Localization and synthesis of alphafoetoprotein in post-implantation mouse embryos.', 'volume': '43', 'author': 'Dziadek', 'year': '1978', 'journal-title': 'J. Embryol. Exp. Morphol.'} / J. Embryol. Exp. Morphol. / Localization and synthesis of alphafoetoprotein in post-implantation mouse embryos. by Dziadek (1978)
10.1002/ar.1091900107
10.1126/science.1350865
10.1016/S0925-4773(97)00664-3
10.1073/pnas.92.5.1292
10.1002/j.1460-2075.1996.tb00601.x / EMBO J. / Identification of tyrosine residues within the intracellular domain of the erythropoietin receptor crucial for STAT5 activation. by Gobert (1996)
10.1242/dev.124.12.2387 / Development / Enhanced cardiogenesis in embryonic stem cells overexpressing the GATA-4 transcription factor. by Grepin (1997)
10.1242/dev.112.2.407 / Development / mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation. by Hebert (1991)
{'key': '2021111508034562000_16.7.784.18', 'first-page': '379', 'article-title': 'Cell interactions and endoderm differentiation in cultured mouse embryos.', 'volume': '62', 'author': 'Hogan', 'year': '1981', 'journal-title': 'J. Embryol. Exp. Morphol.'} / J. Embryol. Exp. Morphol. / Cell interactions and endoderm differentiation in cultured mouse embryos. by Hogan (1981)
10.1016/0012-1606(79)90009-5
10.1242/dev.126.4.723 / Development / The transcription factor Gata6 is essential for early extraembryonic development. by Koutsourakis (1999)
10.1101/gad.11.8.1048
10.1002/j.1460-2075.1986.tb04383.x / EMBO J. / Evidence from molecular cloning that SPARC, a major product of mouse embryo parietal endoderm, is related to an endothelial cell 'culture shock' glycoprotein of Mr 43,000. by Mason (1986)
10.1016/S0925-4773(00)00304-X
10.1101/gad.11.8.1061
10.1006/dbio.1996.0165
10.1101/gad.12.22.3579
10.1074/jbc.M001331200
10.1016/S0925-4773(00)00554-2
10.1006/dbio.1997.8684
10.1128/MCB.19.8.5453 / Mol. Cell. Biol. / The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. by Nishimoto (1999)
10.1101/gad.12.13.2048
10.1038/74199
10.1128/MCB.22.5.1526-1536.2002
10.1242/dev.104.3.431 / Development / The localization of laminin mRNA and protein in the postimplantation embryo and placenta of the mouse: An in situ hybridization and immunocytochemical study. by Senior (1988)
10.1016/0092-8674(76)90114-8
10.1038/343657a0
10.1101/gad.9.21.2635

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 11:04 a.m.)
Indexed	4 days, 11 hours ago (Sept. 3, 2025, 6:46 a.m.)
Issued	23 years, 5 months ago (April 1, 2002)
Published	23 years, 5 months ago (April 1, 2002)
Published Online	23 years, 5 months ago (April 1, 2002)
Published Print	23 years, 5 months ago (April 1, 2002)

Funders 0

None

BibTeX

@article{Fujikura_2002, title={Differentiation of embryonic stem cells is induced by GATA factors}, volume={16}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.968802}, DOI={10.1101/gad.968802}, number={7}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Fujikura, Junji and Yamato, Eiji and Yonemura, Shigenobu and Hosoda, Kiminori and Masui, Shinji and Nakao, Kazuwa and Miyazaki, Jun-ichi and Niwa, Hitoshi}, year={2002}, month=apr, pages={784–789} }

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