Genomics

Dataset Information

297

Microbial-Derived Metabolites Regulate the Colonic Crypt Niche


ABSTRACT: In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem /progenitor cells at their base. We found that the presence of this structure was supported by the physiologic role of a prominent bacterial metabolite, butyrate. This bacterially-produced short chain fatty acid inhibited intestinal epithelial proliferation at physiologic concentrations. During homeostasis, butyrate did not suppress epithelial stem proliferation because it was metabolized by differentiated colonocytes. Provision of butyrate access to stem/progenitor cells either through mucosal injury or application to a crypt-less host led to inhibition of proliferation. The mechanism was dependent on HDAC inhibition in stem cells and the transcription factor Foxo3. Thus, the mammalian crypt unit structure provides energy for differentiated cells at a distance from the crypt base and this action prevents suppression of stem/progenitor proliferation. In total 4 samples were analyzed from 2 independent experiments. Two samples of colonic stem cells treated with 1mM Butyrate and two samples of colonic stem cells treated with 1mM NaCl (mock) as a control

ORGANISM(S): Mus musculus  

SUBMITTER: Eugene M Oltz   Olivia I Koues  Thaddeus S Stappenbeck  Gerard Kaiko  Gerard E Kaiko 

PROVIDER: E-GEOD-74601 | ArrayExpress | 2016-06-27

SECONDARY ACCESSION(S): GSE74601SRP065665PRJNA300945

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate lik  ...[more]

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