Show simple item record

dc.contributor.authorAiroldi, Edoardo Maria
dc.contributor.authorLu, Rong
dc.contributor.authorMarkowetz, Florian
dc.contributor.authorUnwin, Richard
dc.contributor.authorLeek, Jeffrey
dc.contributor.authorMacArthur, Ben
dc.contributor.authorLachmann, Alexander
dc.contributor.authorRozov, Roye
dc.contributor.authorMa’ayan, Avi
dc.contributor.authorBoyer, Laurie
dc.contributor.authorTroyanskaya, Olga
dc.contributor.authorWhetton, Anthony
dc.contributor.authorLemischka, Ihor
dc.date.accessioned2011-09-16T15:22:22Z
dc.date.issued2009
dc.identifier.citationLu, Rong, Florian Markowetz, Richard D. Unwin, Jeffrey T. Leek, Edoardo M. Airoldi, Ben D. MacArthur, Alexander Lachmann, et al. 2009. Systems-level dynamic analyses of fate change in murine embryonic stem cells. Nature 462:358-362.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5133512
dc.description.abstractMolecular regulation of embryonic stem cell (ESC) fate involves a coordinated interaction between epigenetic, transcriptional and translational mechanisms. It is unclear how these different molecular regulatory mechanisms interact to regulate changes in stem cell fate. Here we present a dynamic systems-level study of cell fate change in murine ESCs following a well-defined perturbation. Global changes in histone acetylation, chromatin-bound RNA polymerase II, messenger RNA (mRNA), and nuclear protein levels were measured over 5 days after downregulation of Nanog, a key pluripotency regulator. Our data demonstrate how a single genetic perturbation leads to progressive widespread changes in several molecular regulatory layers, and provide a dynamic view of information flow in the epigenome, transcriptome and proteome. We observe that a large proportion of changes in nuclear protein levels are not accompanied by concordant changes in the expression of corresponding mRNAs, indicating important roles for translational and post-translational regulation of ESC fate. Gene-ontology analysis across different molecular layers indicates that although chromatin reconfiguration is important for altering cell fate, it is preceded by transcription-factor-mediated regulatory events. The temporal order of gene expression alterations shows the order of the regulatory network reconfiguration and offers further insight into the gene regulatory network. Our studies extend the conventional systems biology approach to include many molecular species, regulatory layers and temporal series, and underscore the complexity of the multi-layer regulatory mechanisms responsible for changes in protein expression that determine stem cell fate.en_US
dc.description.sponsorshipStatisticsen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/nature08575en_US
dash.licenseMETA_ONLY
dc.titleSystems-Level Dynamic Analyses of Fate Change in Murine Embryonic Stem Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNatureen_US
dash.depositing.authorAiroldi, Edoardo Maria
dash.embargo.until10000-01-01
dc.identifier.doi10.1038/nature08575*
dash.authorsorderedfalse
dash.contributor.affiliatedAiroldi, Edoardo


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record