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|Title:||Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways||Authors:||Gonzales, Kevin Andrew Uy
|Issue Date:||2015||Source:||Gonzales, K., Liang, H., Lim, Y.-S., Chan, Y.-S., Yeo, J.-C., Tan, C.-P., et al. (2015). Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways. Cell, 162(3), 564-579.||Series/Report no.:||Cell||Abstract:||During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs, including histone acetylation, chromatin remodeling, RNA splicing, and signaling pathways. Strikingly, we detected a strong and specific enrichment of cell-cycle genes involved in DNA replication and G2 phase progression. Genetic and chemical perturbation studies demonstrate that the S and G2 phases attenuate PSD because they possess an intrinsic propensity toward the pluripotent state that is independent of G1 phase. Our data therefore functionally establish that pluripotency control is hardwired to the cell-cycle machinery, where S and G2 phase-specific pathways deterministically restrict PSD, whereas the absence of such pathways in G1 phase potentially permits the initiation of differentiation.||URI:||https://hdl.handle.net/10356/103694
|ISSN:||0092-8674||DOI:||http://dx.doi.org/10.1016/j.cell.2015.07.001||Rights:||© 2015 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Cell, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.cell.2015.07.001].||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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