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Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

dc.contributor.authorHayakawa, Yoku
dc.contributor.authorAriyama, Hiroshi
dc.contributor.authorStancikova, Jitka
dc.contributor.authorSakitani, Kosuke
dc.contributor.authorAsfaha, Samuel
dc.contributor.authorRenz, Bernhard W.
dc.contributor.authorDubeykovskaya, Zinaida A.
dc.contributor.authorShibata, Wataru
dc.contributor.authorWang, Hongshan
dc.contributor.authorWestphalen, Christoph B.
dc.contributor.authorChen, Xiaowei
dc.contributor.authorTakemoto, Yoshihiro
dc.contributor.authorKim, Woosook
dc.contributor.authorKhurana, Shradha S.
dc.contributor.authorTailor, Yagnesh
dc.contributor.authorNagar, Karan
dc.contributor.authorTomita, Hiroyuki
dc.contributor.authorHara, Akira
dc.contributor.authorSepulveda, Antonia R.
dc.contributor.authorSetlik, Wanda
dc.contributor.authorGershon, Michael D.
dc.contributor.authorSaha, Subhrajit
dc.contributor.authorDing, Lei
dc.contributor.authorFriedman, Richard A.
dc.contributor.authorKonieczny, Stephen F.
dc.contributor.authorWorthley, Daniel L.
dc.contributor.authorKorinek, Vladimir
dc.contributor.authorWang, Timothy C.
dc.contributor.authorShen, Zeli
dc.contributor.authorFox, James G
dc.date.accessioned2017-03-29T16:17:09Z
dc.date.available2017-03-29T16:17:09Z
dc.date.issued2015-11
dc.date.submitted2015-08
dc.identifier.issn1535-6108
dc.identifier.urihttp://hdl.handle.net/1721.1/107766
dc.description.abstractThe regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1⁺ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12⁺ endothelial cells and Cxcr4⁺ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grants 54CA126513, R01CA093405, R01CA120979, and R01DK052778)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.ccell.2015.10.003en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleMist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Nicheen_US
dc.typeArticleen_US
dc.identifier.citationHayakawa, Yoku et al. “Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.” Cancer Cell 28.6 (2015): 800–814.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Division of Comparative Medicineen_US
dc.contributor.mitauthorShen, Zeli
dc.contributor.mitauthorFox, James G
dc.relation.journalCancer Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W.; Dubeykovskaya, Zinaida A.; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B.; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S.; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R.; Setlik, Wanda; Gershon, Michael D.; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G.; Friedman, Richard A.; Konieczny, Stephen F.; Worthley, Daniel L.; Korinek, Vladimir; Wang, Timothy C.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-9307-6116
mit.licensePUBLISHER_CCen_US


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