Format

Send to

Choose Destination
Nat Cell Biol. 2012 Oct;14(10):1099-1104. doi: 10.1038/ncb2581. Epub 2012 Sep 23.

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

Author information

1
Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
2
Dept. of Physics & Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
3
Institute of Medical Biology, 06-06 Immunos, Singapore.
4
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
5
UMC Utrecht, Dept. of Immunology and Cell Biology, PO BOX 85090, 3508AB Utrecht, Netherlands.
#
Contributed equally

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.

PMID:
23000963
PMCID:
PMC3789123
DOI:
10.1038/ncb2581
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center