Abstract:
:We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state.
journal_name
Cell Systjournal_title
Cell systemsauthors
Ding L,Paszkowski-Rogacz M,Winzi M,Chakraborty D,Theis M,Singh S,Ciotta G,Poser I,Roguev A,Chu WK,Choudhary C,Mann M,Stewart AF,Krogan N,Buchholz Fdoi
10.1016/j.cels.2015.08.002subject
Has Abstractpub_date
2015-08-26 00:00:00pages
141-51issue
2eissn
2405-4712issn
2405-4720pii
S2405-4712(15)00055-1journal_volume
1pub_type
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