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

Document Type

Article

Publication Date

5-12-2015

Institution/Department

Molecular Medicine, MMCRI

Journal Title

The EMBO journal

MeSH Headings

Animals, Apoptosis, Cell Differentiation, Cell Lineage, Intestines, Membrane Glycoproteins, Mice, Mice, Knockout, Signal Transduction, Snail Family Transcription Factors, Transcription Factors

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.

ISSN

1460-2075

First Page

1319

Last Page

1335

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