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Oct-4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells
Open accessAbstract
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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Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
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Testicular germ-cell tumours in a broader perspective
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Pax6 is a human neuroectoderm cell fate determinant
Zhang, X., Huang, C. T., Chen, J., Pankratz, M. T., Xi, J., Li, J., Yang, Y., LaVaute, T. M., Li, X.-J., Ayala, M., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.04.017 · Cited by 480
Hay, D. C., Zhao, D., Fletcher, J., Hewitt, Z. A., McLean, D., Urruticoechea-Uriguen, A., Black, J. R., Elcombe, C., Ross, J. A., Wolf, R., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0718 · Cited by 441
Self-citation
Metadata
- Authors
- Hay, D. C., Sutherland, L., Clark, J., & Burdon, T.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- 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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