B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

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B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

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dc.contributor.author Tarasov, Kirill V.
dc.contributor.author Tarasova, Yelena S.
dc.contributor.author Tam, Wai Leong
dc.contributor.author Riordon, Daniel R.
dc.contributor.author Elliott, Steven T.
dc.contributor.author Kania, Gabriela
dc.contributor.author Li, Jinliang
dc.contributor.author Yamanaka, Satoshi
dc.contributor.author Crider, David G.
dc.contributor.author Testa, Gianluca
dc.contributor.author Li, Ronald A.
dc.contributor.author Stewart, Colin L.
dc.contributor.author Liu, Yie
dc.contributor.author Van Eyk, Jennifer E.
dc.contributor.author Wersto, Robert P.
dc.contributor.author Wobus, Anna M.
dc.contributor.author Boheler, Kenneth R.
dc.contributor.author Lim, Bing
dc.date.accessioned 2012-01-14T22:04:05Z
dc.date.issued 2008
dc.identifier.citation Tarasov, Kirill V., Yelena S. Tarasova, Wai Leong Tam, Daniel R. Riordon, Steven T. Elliott, Gabriela Kania, Jinliang Li, et al. 2008. B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells. PLoS ONE 3(6): e2478. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:7628330
dc.description.abstract Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0002478 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423619/pdf/ en_US
dash.license LAA
dc.subject cell biology en_US
dc.subject cell growth and division en_US
dc.subject developmental biology en_US
dc.subject stem cells en_US
dc.title B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Lim, Bing
dc.date.available 2012-01-14T22:04:05Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US

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