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dc.contributor.authorGoodfellow, Marc
dc.contributor.authorManning, Cerys
dc.contributor.authorPapalopulu, Nancy
dc.contributor.authorGalla, Tobias
dc.contributor.authorPhillips, Nicholas E.
dc.date.accessioned2014-07-04T11:47:54Z
dc.date.issued2014
dc.description.abstractProgenitor maintenance, timed differentiation and the potential to enter quiescence are three fundamental processes that underlie the development of any organ system. In the nervous system, progenitor cells show short-period oscillations in the expression of the transcriptional repressor Hes1, while neurons and quiescent progenitors show stable low and high levels of Hes1, respectively. Here we use experimental data to develop a mathematical model of the double-negative interaction between Hes1 and a microRNA, miR-9, with the aim of understanding how cells transition from one state to another. We show that the input of miR-9 into the Hes1 oscillator tunes its oscillatory dynamics, and endows the system with bistability and the ability to measure time to differentiation. Our results suggest that a relatively simple and widespread network of cross-repressive interactions provides a unifying framework for progenitor maintenance, the timing of differentiation and the emergence of alternative cell states.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.identifier.citationVol. 5, Article 3399en_GB
dc.identifier.doi10.1038/ncomms4399
dc.identifier.grantnumberWT090868en_GB
dc.identifier.urihttp://hdl.handle.net/10871/15142
dc.language.isoenen_GB
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttp://dx.doi.org/10.1038/ncomms4399en_GB
dc.relation.urlhttp://www.nature.com/ncomms/2014/140304/ncomms4399/full/ncomms4399.htmlen_GB
dc.rightsThis work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/en_GB
dc.titlemicroRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.en_GB
dc.typeArticleen_GB
dc.date.available2014-07-04T11:47:54Z
exeter.place-of-publicationEngland
dc.description© 2014 Macmillan Publishers Limiteden_GB
dc.descriptionThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.en_GB
dc.identifier.eissn2041-1723
dc.identifier.journalNature Communicationsen_GB


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