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Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE148943 | GEO | 2020/04/21

REPOSITORIES: GEO

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Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells [ATAC-Seq]

Project description:The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we demonstrate that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin’s transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by intrinsic and extrinsic stress signalling results in a process resembling aberrant "villisation" of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires discrete regulation of transcription by transcriptional co-factors.

2020-04-21 | GSE148940 | GEO

Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells [scRNA-Seq]

2020-04-21 | GSE148942 | GEO

Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells [RNA-Seq]

2020-04-21 | GSE148941 | GEO