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. 2025 Jun 5;32(6):952-969.e8.
doi: 10.1016/j.stem.2025.03.005. Epub 2025 Apr 8.

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell

Swarnabh Bhattacharya  1 , Guodong Tie  2 , Pratik N P Singh  1 , Ermanno Malagola  3 , Onur Eskiocak  4 , Ruiyang He  2 , Judith Kraiczy  1 , Wei Gu  5 , Yakov Perlov  2 , Aybuke Alici-Garipcan  6 , Semir Beyaz  6 , Timothy C Wang  3 , Qiao Zhou  5 , Ramesh A Shivdasani  7
Affiliations

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell

Swarnabh Bhattacharya et al. Cell Stem Cell. .

Abstract

Enterocytes and four classic secretory cell types derive from intestinal epithelial stem cells. Based on morphology, location, and canonical markers, goblet and Paneth cells are considered distinct secretory types. Here, we report high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of their enteroendocrine or tuft cell siblings. Mouse and human goblet and Paneth cells express extraordinary fractions of few antimicrobial genes, which reflect specific responses to local niches. Wnt signaling retains some ATOH1+ secretory cells in crypt bottoms, where the absence of BMP signaling potently induces Paneth features. Cells that migrate away from crypt bottoms encounter BMPs and thereby acquire goblet properties. These phenotypes and underlying accessible cis-elements interconvert in post-mitotic cells. Thus, goblet and Paneth properties represent alternative phenotypic manifestations of a common signal-responsive terminal cell type. These findings reveal exquisite niche-dependent cell plasticity and cis-regulatory dynamics in likely response to antimicrobial needs.

Keywords: Paneth cells; epigenetic control of cell properties; goblet cells; intestinal epithelial differentiation; intestinal stem cells; lineage plasticity.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

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