Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

被引：419

作者：

Stange, Daniel E. ^{[1
,2
,3
]}

Koo, Bon-Kyoung ^{[1
,2
,4
]}

Huch, Meritxell ^{[1
,2
]}

Sibbel, Greg ^{[5
]}

Basak, Onur ^{[1
,2
]}

Lyubimova, Anna ^{[1
,2
,6
]}

Kujala, Pekka ^{[7
]}

Bartfeld, Sina ^{[1
,2
]}

Koster, Jan ^{[8
]}

Geahlen, Jessica H. ^{[5
]}

Peters, Peter J. ^{[7
]}

van Es, Johan H. ^{[1
,2
]}

van de Wetering, Marc ^{[1
,2
]}

Mills, Jason C. ^{[5
]}

Clevers, Hans ^{[1
,2
]}

机构：

[1] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[3] Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Gen Thorac & Vasc Surg, D-01307 Dresden, Germany

[4] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1QR, England

[5] Washington Univ, Sch Med, Dept Med, Div Gastroenterol, St Louis, MO 63110 USA

[6] MIT, Dept Phys & Biol, Cambridge, MA 02139 USA

[7] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Cell Biol 2, NL-1066 CX Amsterdam, Netherlands

[8] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1100 DE Amsterdam, Netherlands

来源：

CELL | 2013年 / 155卷 / 02期

基金：

英国惠康基金; 新加坡国家研究基金会; 欧洲研究理事会;

关键词：

RECEPTOR FAMILY-MEMBER; MOUSE STOMACH; ZYMOGENIC CELLS; LIVER-REGENERATION; PROGENITOR CELLS; SMALL-INTESTINE; PARIETAL-CELLS; ADULT STEM; IN-VITRO; METAPLASIA;

D O I：

10.1016/j.cell.2013.09.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bidirectionally toward pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy(+) chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent "reserve" stem cells. These observations challenge the notion that stem cell hierarchies represent a "one-way street."

引用

页码：357 / 368

页数：12

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