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Publication : The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression.

First Author  Osorno R Year  2012
Journal  Development Volume  139
Issue  13 Pages  2288-98
PubMed ID  22669820 Mgi Jnum  J:314890
Mgi Id  MGI:6822396 Doi  10.1242/dev.078071
Citation  Osorno R, et al. (2012) The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression. Development 139(13):2288-98
abstractText  The transcription factors Nanog and Oct4 regulate pluripotency in the pre-implantation epiblast and in derivative embryonic stem cells. During post-implantation development, the precise timing and mechanism of the loss of pluripotency is unknown. Here, we show that in the mouse, pluripotency is extinguished at the onset of somitogenesis, coincident with reduced expression and chromatin accessibility of Oct4 and Nanog regulatory regions. Prior to somitogenesis expression of both Nanog and Oct4 is regionalized. We show that pluripotency tracks the in vivo level of Oct4 and not Nanog by assessing the ability to reactivate or maintain Nanog expression in cell culture. Enforced Oct4 expression in somitogenesis-stage tissue provokes rapid reopening of Oct4 and Nanog chromatin, Nanog re-expression and resuscitates moribund pluripotency. Our data suggest that decreasing Oct4 expression is converted to a sudden drop in competence to maintain pluripotency gene regulatory network activity that is subsequently stabilized by epigenetic locks.
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