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EMBO J. 2015 May 12;34(10):1319-35. doi: 10.15252/embj.201490881. Epub 2015 Mar 10.

Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.

Author information

1
Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.
2
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia.
3
Australian Centre for Blood Diseases, Monash University & Alfred Health, Melbourne, Vic., Australia Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
4
Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia Australian Regenerative Medicine Institute, Monash University, Clayton, Vic., Australia.
5
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
6
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Molecular and Cellular Oncology, Inflammation Research Center, VIB, Ghent, Belgium.
7
A*STAR Institute of Medical Biology, Singapore City, Singapore.
8
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia g.hime@unimelb.edu.au helen.abud@monash.edu.
9
Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia g.hime@unimelb.edu.au helen.abud@monash.edu.

Abstract

Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage.

KEYWORDS:

SerinC3; Snail; apoptosis; intestinal stem cell; organoid

PMID:
25759216
PMCID:
PMC4491994
DOI:
10.15252/embj.201490881
[Indexed for MEDLINE]
Free PMC Article

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