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Oct-4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells

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Hay, David C., Sutherland, Linda, Clark, John, Burdon, Tom·2004·Stem Cells

Abstract

The transcription factor Oct-4 is a marker of pluripotency in mouse and human embryonic stem (ES) cells. Previous studies using a tetracycline-regulated Oct-4 transgene in the ZHBTc4 cell line demonstrated that downregulation of Oct-4 expression induced dedifferentiation into trophoblast, a lineage mouse ES cells do not normally generate. We found that transfection of Oct-4-specific short interfering RNA significantly reduced expression and functional activity of Oct-4 in mouse and human ES cells, enabling its role to be compared in both cell types. In mouse ES cells, Oct-4 knockdown produced a pattern of morphological differentiation and increase in expression of the trophoblast-associated transcription factor Cdx2, similar to that triggered by suppressing the Oct-4 transgene in the ZHBTc4 cell line. In addition, downregulation of Oct-4 was accompanied by increased expression of the endoderm-associated genes Gata6 and α-fetoprotein, and a gene trap associated with primitive liver/yolk sac differentiation. In human ES cells, Oct-4 knockdown also induced morphological differentiation coincident with the upregulation of Gata6. The induction of Cdx2 and other trophoblast-associated genes, however, was dependent on the culture conditions. These results establish the general requirement for Oct-4 in maintaining pluripotency in ES cells. Moreover, the upregulation of endoderm-associated markers in both mouse and human ES cells points to overlap between development of trophoblast and endoderm differentiation.

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Metadata

Authors
Hay, D. C., Sutherland, L., Clark, J., & Burdon, T.
Venue
Stem Cells
Published
2004-03-01
Volume
22
Issue
2
Pages
225-235
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
OpenAlex
W2061004792
Cited by
375
References
25
FWCI
10.28
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Oct-4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells. https://app.cochat.ai/papers/10.1634/stemcells.22-2-225
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Hay, D. C., Sutherland, L., Clark, J., & Burdon, T. (2004). Oct-4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells. Stem Cells. https://doi.org/10.1634/stemcells.22-2-225

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