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Publication : The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon.

First Author  Dinsart G Year  2024
Journal  EMBO Rep Volume  25
Issue  1 Pages  304-333
PubMed ID  38177905 Mgi Jnum  J:360537
Mgi Id  MGI:7609917 Doi  10.1038/s44319-023-00013-5
Citation  Dinsart G, et al. (2024) The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon. EMBO Rep 25(1):304-333
abstractText  The gastrointestinal epithelium constitutes a chemosensory system for microbiota-derived metabolites such as short-chain fatty acids (SCFA). Here, we investigate the spatial distribution of Olfr78, one of the SCFA receptors, in the mouse intestine and study the transcriptome of colon enteroendocrine cells expressing Olfr78. The receptor is predominantly detected in the enterochromaffin and L subtypes in the proximal and distal colon, respectively. Using the Olfr78-GFP and VilCre/Olfr78flox transgenic mouse lines, we show that loss of epithelial Olfr78 results in impaired enterochromaffin cell differentiation, blocking cells in an undefined secretory lineage state. This is accompanied by a reduced defense response to bacteria in colon crypts and slight dysbiosis. Using organoid cultures, we further show that maintenance of enterochromaffin cells involves activation of the Olfr78 receptor via the SCFA ligand acetate. Taken together, our work provides evidence that Olfr78 contributes to colon homeostasis by promoting enterochromaffin cell differentiation.
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