Dll1+ Secretory Progenitor Cells Revert to Stem Cells Upon Crypt Damage

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2012 Sep 25

PMID 23000963

Citations 402

Authors

Johan H van Es

Toshiro Sato

Marc van de Wetering

Anna Lyubimova

Annie Ng Yee Nee

Alex Gregorieff

Nobuo Sasaki

Laura Zeinstra

Maaike van den Born

Jeroen Korving

Anton C M Martens

Nick Barker

Alexander van Oudenaarden

Hans Clevers

Affiliations

Soon will be listed here.

Abstract

Lgr5+ intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dll1 is expressed by a subset of immediate stem cell daughters. Lineage tracing in Dll1(GFP-ires-CreERT2) knock-in 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 Dll1(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.

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