The University of Southampton
University of Southampton Institutional Repository

Systems-level dynamic analyses of fate change in murine embryonic stem cells

Record type: Article

Molecular 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 multilayer regulatory mechanisms responsible for changes in protein expression that determine stem cell fate

Full text not available from this repository.

Citation

Lu, Rong, Markowetz, Florian, Unwin, Richard D., Leek, Jeffrey T., Airoldi, Edoardo M., MacArthur, Ben D., Lachmann, Alexander, Rozov, Roye, Ma’ayan, Avi, Boyer, Laurie A., Troyanskaya, Olga G., Whetton, Anthony D. and Lemischka, Ihor R. (2009) Systems-level dynamic analyses of fate change in murine embryonic stem cells Nature, 462, (7271), pp. 358-362. (doi:10.1038/nature08575). (PMID:19924215).

More information

Published date: 2009
Organisations: Medicine, Mathematics

Identifiers

Local EPrints ID: 175701
URI: http://eprints.soton.ac.uk/id/eprint/175701
ISSN: 0028-0836
PURE UUID: acb099a7-c3c7-46d2-bd75-e736688a40cf

Catalogue record

Date deposited: 25 Feb 2011 14:49
Last modified: 18 Jul 2017 12:09

Export record

Altmetrics

Contributors

Author: Rong Lu
Author: Florian Markowetz
Author: Richard D. Unwin
Author: Jeffrey T. Leek
Author: Edoardo M. Airoldi
Author: Alexander Lachmann
Author: Roye Rozov
Author: Avi Ma’ayan
Author: Laurie A. Boyer
Author: Olga G. Troyanskaya
Author: Anthony D. Whetton
Author: Ihor R. Lemischka

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×