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dc.contributor.authorMead, Benjamin E
dc.contributor.authorHattori, Kazuki
dc.contributor.authorLevy, Lauren
dc.contributor.authorImada, Shinya
dc.contributor.authorGoto, Norihiro
dc.contributor.authorVukovic, Marko
dc.contributor.authorSze, Daphne
dc.contributor.authorKummerlowe, Conner
dc.contributor.authorMatute, Juan D
dc.contributor.authorDuan, Jinzhi
dc.contributor.authorLanger, Robert
dc.contributor.authorBlumberg, Richard S
dc.contributor.authorOrdovas-Montanes, Jose
dc.contributor.authorYilmaz, Ömer H
dc.contributor.authorKarp, Jeffrey M
dc.contributor.authorShalek, Alex K
dc.date.accessioned2023-01-10T17:38:38Z
dc.date.available2023-01-10T17:38:38Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/147041
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the nuclear exporter Exportin 1 modulate the fate of intestinal stem cells, independently of known differentiation cues, significantly increasing the abundance of Paneth cells in the organoids and in wild-type mice. Physiological organoid models of the differentiation of intestinal stem cells could find broader utility for the screening of biological targets and small molecules that can modulate the composition and function of other barrier epithelia.</jats:p>en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1038/S41551-022-00863-9en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNatureen_US
dc.titleScreening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiationen_US
dc.typeArticleen_US
dc.identifier.citationMead, Benjamin E, Hattori, Kazuki, Levy, Lauren, Imada, Shinya, Goto, Norihiro et al. 2022. "Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiation." Nature Biomedical Engineering, 6 (4).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalNature Biomedical Engineeringen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-01-10T17:25:43Z
dspace.orderedauthorsMead, BE; Hattori, K; Levy, L; Imada, S; Goto, N; Vukovic, M; Sze, D; Kummerlowe, C; Matute, JD; Duan, J; Langer, R; Blumberg, RS; Ordovas-Montanes, J; Yilmaz, ÖH; Karp, JM; Shalek, AKen_US
dspace.date.submission2023-01-10T17:25:58Z
mit.journal.volume6en_US
mit.journal.issue4en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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