Expression data from human foreskin fibroblast and human iduced pluripotent stem cell
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE135409 | GEO | 2019/08/06
REPOSITORIES: GEO
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Project description:In recent years, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, although the role of the major heterochromatin proteins in pluripotency remains largely unknown. Here we identify heterochromatin protein 1-beta (HP1β) to be differentially localized and associated with chromatin in pluripotent and differentiated cells, to be essential for proper ESC differentiation as well as for the maintenance of the pluripotent state. Microscopy analysis supported by biochemical fractionations and chromatin immunoprecipitation (ChIP) experiments demonstrate that unlike its prominent localization in heterochromatic chromocenters in differentiated cells, HP1β is diffuse in the ESC nucleoplasm, poorly bound to chromatin, and highly expressed. The fraction of HP1β that does associate with chromatin in ESCs is highly enriched in genic regions. HP1β-knockout ESCs but not HP1α knockout ESCs exhibit a loss of the morphological and proliferative characteristics of embryonic pluripotent cells. HP1β depletion in ESCs results in reduced expression of pluripotency factors and aberrant differentiation. In contrast, HP1β depletion in differentiated cells perturbs the maintenance of differentiation, and facilitates reprogramming to induced pluripotent stem cells. Our results demonstrate a dual role for HP1β, in ESCs it is essential for pluripotency maintenance, and in differentiated cells for proper differentiation. ChIP-Seq of HP1β in mouse embryonic stem cells.
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Project description:Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem-cell states. The two states that bookend the pluripotency continuum, naïve and primed, are well characterized, but our understanding of the intermediate states and transitions between them remain incomplete. Here, we dissect the dynamics of pluripotent state transitions underlying pre- to post-implantation epiblast differentiation. Through comprehensive mapping of the proteome, phosphoproteome, transcriptome, and epigenome of embryonic stem cells transitioning from naïve to primed pluripotency, we find that rapid, acute, and widespread changes to the phosphoproteome precede ordered changes to the epigenome, transcriptome, and proteome. Reconstruction of kinase-substrate networks reveals signaling cascades, dynamics, and crosstalk. Distinct waves of global proteomic changes mark discrete phases of pluripotency, with cell state-specific surface markers tracking pluripotent state transitions. Our data provide new insights into the multi-layered control of the phased progression of pluripotency and a foundation for modeling mechanisms regulating pluripotent state transitions (www.stemcellatlasorg).
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