Dll1+ secretory progenitor cells revert to stem cells upon crypt damage

被引：576

作者：

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

Sato, Toshiro ^{[1
,2
]}

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

Lyubimova, Anna ^{[3
]}

Nee, Annie Ng Yee ^{[4
]}

Gregorieff, Alex ^{[5
]}

Sasaki, Nobuo ^{[1
,2
]}

Zeinstra, Laura ^{[1
,2
]}

van den Born, Maaike ^{[1
,2
]}

Korving, Jeroen ^{[1
,2
]}

Martens, Anton C. M. ^{[6
,7
]}

Barker, Nick ^{[4
]}

van Oudenaarden, Alexander ^{[3
]}

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

[4] Inst Med Biol, Singapore, Singapore

[5] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[6] UMC Utrecht, Dept Immunol, NL-3508 AB Utrecht, Netherlands

[7] UMC Utrecht, Dept Cell Biol, NL-3508 AB Utrecht, Netherlands

来源：

NATURE CELL BIOLOGY | 2012年 / 14卷 / 10期

关键词：

MOUSE SMALL INTESTINE; ORIGIN; GENE; EXPRESSION; DIFFERENTIATION; POPULATION; COMMITMENT; RENEWAL; MARKER; MATH1;

D O I：

10.1038/ncb2581

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Lgr5(+) intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dill is expressed by a subset of immediate stem cell daughters. Lineage tracing in Dll1(GFP-ires-CreERT2) mice reveals that single Dll1(high) cells generate small, short-lived clones containing all four secretory cell types. Lineage specification thus occurs in immediate stem cell daughters through Notch lateral inhibition. Cultured Dll(1)high cells form long-lived organoids (mini-guts) on brief Wnt3A exposure. When Dll1(high) cells are genetically marked before tissue damage, stem cell tracing events occur. Thus, secretory progenitors exhibit plasticity by regaining stemness on damage.

引用

页码：1099 / +

页数：12

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