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Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency. | LitMetric

Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.

Cell Stem Cell

Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK; Department of Molecular Biology, Faculty of Science, Radboud University, 6525GA Nijmegen, the Netherlands. Electronic address:

Published: May 2019

AI Article Synopsis

Article Abstract

The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. Here, we delineate additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switches activity from supporting self-renewal and undergoes genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevents re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. Triple deletion of Etv5, Rbpj, and Tcf3 disables ESCs, such that they remain largely undifferentiated and locked in self-renewal, even in the presence of differentiation stimuli. Thus, genetic elimination of three complementary drivers of network transition stalls developmental progression, emulating environmental insulation by small-molecule inhibitors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509416PMC
http://dx.doi.org/10.1016/j.stem.2019.03.017DOI Listing

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