File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells

TitleB-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells
Authors
Issue Date2008
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2008, v. 3 n. 6 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/91694
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Intramural Research Program of the NIA/NIHR01 HL72857
German Research FoundationWo 503/3-3
Funding Information:

This research was supported by the Intramural Research Program of the NIA/NIH (KRB, RPW), the German Research Foundation (Wo 503/3-3: AMW), and NIH grants (R01 HL72857: RAL).

References

 

DC FieldValueLanguage
dc.contributor.authorTarasov, KVen_HK
dc.contributor.authorTarasova, YSen_HK
dc.contributor.authorTam, WLen_HK
dc.contributor.authorRiordon, DRen_HK
dc.contributor.authorElliott, STen_HK
dc.contributor.authorKania, Gen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorYamanaka, Sen_HK
dc.contributor.authorCrider, DGen_HK
dc.contributor.authorTesta, Gen_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorLim, Ben_HK
dc.contributor.authorStewart, CLen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorVan Eyk, JEen_HK
dc.contributor.authorWersto, RPen_HK
dc.contributor.authorWobus, AMen_HK
dc.contributor.authorBoheler, KRen_HK
dc.date.accessioned2010-09-17T10:23:27Z-
dc.date.available2010-09-17T10:23:27Z-
dc.date.issued2008en_HK
dc.identifier.citationPlos One, 2008, v. 3 n. 6en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91694-
dc.description.abstractBackground: 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_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCell Cycle - physiology-
dc.subject.meshChromosomal Instability-
dc.subject.meshEmbryonic Stem Cells - cytology-
dc.subject.meshGenes, myb-
dc.subject.meshProto-Oncogene Proteins c-myb - genetics - physiology-
dc.titleB-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=3&issue=6, article no. e2478&spage=&epage=&date=2008&atitle=B-MYB+is+essential+for+normal+cell+cycle+progression+and+chromosomal+stability+of+embryonic+stem+cells-
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0002478en_HK
dc.identifier.pmid18575582en_HK
dc.identifier.pmcidPMC2423619-
dc.identifier.scopuseid_2-s2.0-49649113886en_HK
dc.identifier.hkuros183038-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-49649113886&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume3en_HK
dc.identifier.issue6en_HK
dc.identifier.isiWOS:000263288000009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTarasov, KV=7003759886en_HK
dc.identifier.scopusauthoridTarasova, YS=8730977100en_HK
dc.identifier.scopusauthoridTam, WL=7102605570en_HK
dc.identifier.scopusauthoridRiordon, DR=6508113678en_HK
dc.identifier.scopusauthoridElliott, ST=8627413000en_HK
dc.identifier.scopusauthoridKania, G=6603849130en_HK
dc.identifier.scopusauthoridLi, J=35071405700en_HK
dc.identifier.scopusauthoridYamanaka, S=36933037500en_HK
dc.identifier.scopusauthoridCrider, DG=8730977000en_HK
dc.identifier.scopusauthoridTesta, G=24464588400en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridLim, B=7201984111en_HK
dc.identifier.scopusauthoridStewart, CL=7401937591en_HK
dc.identifier.scopusauthoridLiu, Y=12446248600en_HK
dc.identifier.scopusauthoridVan Eyk, JE=7004835259en_HK
dc.identifier.scopusauthoridWersto, RP=7003348061en_HK
dc.identifier.scopusauthoridWobus, AM=7005287845en_HK
dc.identifier.scopusauthoridBoheler, KR=7005975654en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats