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Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages

Lookup NU author(s): Dr Louise Hyslop, Professor Miodrag Stojkovic, Professor Lyle Armstrong, Theresia Walter, Petra Stojkovic, Professor Mary Herbert, Professor Alison Murdoch, Professor Tom Strachan, Professor Majlinda Lako

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Abstract

The homeobox transcription factor Nanog has been proposed to play a crucial role in the maintenance of the undifferentiated state of murine embryonic stem cells. A human counterpart, NANOG, has been identified, but its function and localization have not hitherto been described. We have used a combination of RNA interference and quantitative real-time polymerase chain reaction to study NANOG in human embryonic stem and embryonic carcinoma cells. Transfection of NANOG-specific small interfering RNAs reduced levels of NANOG transcript and protein and induced activation of the extraembryonic endoderm-associated genes GATA4, GATA6, LAMININ B1, and AFP as well as upregulation of trophectoderm-associated genes CDX2, GATA2, hCG-alpha, and ACG-beta. Immunostaining of preimplantation human embryos showed that NANOG was expressed in the inner cell mass of expanded blastocysts but not in earlier-stage embryos, consistent with a role in the maintenance of pluripotency. Taken together, our findings suggest that NANOG acts as a gate-keeper of pluripotency in human embryonic stem and carcinoma cells by preventing their differentiation to extraembryonic endoderm and trophectoderm lineages. © AlphaMed Press.


Publication metadata

Author(s): Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2005

Volume: 23

Issue: 8

Pages: 1035-1043

Print publication date: 01/09/2005

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: http://dx.doi.org/10.1634/stemcells.2005-0080

DOI: 10.1634/stemcells.2005-0080

PubMed id: 15983365


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