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

Bhattacharya, Swarnabh, Tie, Guodong, Singh, Pratik NP, Malagola, Ermanno, Eskiocak, Onur, He, Ruiyang, Kraiczy, Judith, Gu, Wei, Perlov, Yakov, Alici-Garipcan, Aybuke, Beyaz, Semir, Wang, Timothy C, Zhou, Qiao, Shivdasani, Ramesh A (April 2025) Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell. Cell Stem Cell. ISSN 1934-5909 (Public Dataset)

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.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics
CSHL Authors:
Communities: CSHL labs > Beyaz lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 1 April 2025
Date Deposited: 14 Apr 2025 12:08
Last Modified: 14 Apr 2025 12:08
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/41846

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