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Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells.
Stem Cells. 2007 Feb; 25(2):500-10.SC

Abstract

The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans.

Authors+Show Affiliations

Roslin Institute, Department of Gene Function and Development, Roslin, Midlothian, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17068183

Citation

Babaie, Yasmin, et al. "Analysis of Oct4-dependent Transcriptional Networks Regulating Self-renewal and Pluripotency in Human Embryonic Stem Cells." Stem Cells (Dayton, Ohio), vol. 25, no. 2, 2007, pp. 500-10.
Babaie Y, Herwig R, Greber B, et al. Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells. 2007;25(2):500-10.
Babaie, Y., Herwig, R., Greber, B., Brink, T. C., Wruck, W., Groth, D., Lehrach, H., Burdon, T., & Adjaye, J. (2007). Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells (Dayton, Ohio), 25(2), 500-10.
Babaie Y, et al. Analysis of Oct4-dependent Transcriptional Networks Regulating Self-renewal and Pluripotency in Human Embryonic Stem Cells. Stem Cells. 2007;25(2):500-10. PubMed PMID: 17068183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. AU - Babaie,Yasmin, AU - Herwig,Ralf, AU - Greber,Boris, AU - Brink,Thore C, AU - Wruck,Wasco, AU - Groth,Detlef, AU - Lehrach,Hans, AU - Burdon,Tom, AU - Adjaye,James, Y1 - 2006/10/26/ PY - 2006/10/28/pubmed PY - 2007/3/16/medline PY - 2006/10/28/entrez SP - 500 EP - 10 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 25 IS - 2 N2 - The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans. SN - 1066-5099 UR - https://www.unboundmedicine.com/medline/citation/17068183/Analysis_of_Oct4_dependent_transcriptional_networks_regulating_self_renewal_and_pluripotency_in_human_embryonic_stem_cells_ L2 - https://doi.org/10.1634/stemcells.2006-0426 DB - PRIME DP - Unbound Medicine ER -