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dc.contributor.authorItzkovitz, Shaul Shalev
dc.contributor.authorBlat, Irene C.
dc.contributor.authorClevers, Hans
dc.contributor.authorvan Oudenaarden, Alexander
dc.contributor.authorJacks, Tyler E.
dc.contributor.authorvan Oudenaarden, Alexander
dc.date.accessioned2014-12-10T16:12:42Z
dc.date.available2014-12-10T16:12:42Z
dc.date.issued2012-02
dc.date.submitted2011-09
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/92250
dc.description.abstractIntestinal crypts in mammals are comprised of long-lived stem cells and shorter-lived progenies. These two populations are maintained in specific proportions during adult life. Here, we investigate the design principles governing the dynamics of these proportions during crypt morphogenesis. Using optimal control theory, we show that a proliferation strategy known as a “bang-bang” control minimizes the time to obtain a mature crypt. This strategy consists of a surge of symmetric stem cell divisions, establishing the entire stem cell pool first, followed by a sharp transition to strictly asymmetric stem cell divisions, producing nonstem cells with a delay. We validate these predictions using lineage tracing and single-molecule fluorescence in situ hybridization of intestinal crypts in infant mice, uncovering small crypts that are entirely composed of Lgr5-labeled stem cells, which become a minority as crypts continue to grow. Our approach can be used to uncover similar design principles in other developmental systems.en_US
dc.description.sponsorshipNational Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.). Pioneer Award (1DP1OD003936)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)en_US
dc.description.sponsorshipMachiah Foundationen_US
dc.description.sponsorshipHuman Frontier Science Program (Strasbourg, France)en_US
dc.description.sponsorshipHoward Hughes Medical Institute (Gilliam Fellowship)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2011.12.025en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevieren_US
dc.titleOptimality in the Development of Intestinal Cryptsen_US
dc.typeArticleen_US
dc.identifier.citationItzkovitz, Shalev, Irene C. Blat, Tyler Jacks, Hans Clevers, and Alexander van Oudenaarden. “Optimality in the Development of Intestinal Crypts.” Cell 148, no. 3 (February 2012): 608–619. © 2012 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorItzkovitz, Shaul Shaleven_US
dc.contributor.mitauthorvan Oudenaarden, Alexanderen_US
dc.contributor.mitauthorBlat, Irene C.en_US
dc.contributor.mitauthorJacks, Tyler E.en_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsItzkovitz, Shalev; Blat, Irene C.; Jacks, Tyler; Clevers, Hans; van Oudenaarden, Alexanderen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-5785-8911
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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