Niche-driven phenotypic plasticity and cis-regulatory dynamics of a revised model for intestinal secretory differentiation.

Bhattacharya, Swarnabh, Tei, Guodong, Singh, Pratik Narendra Pratap, Malagola, Ermanno, Eskiocak, Onur, He, Ruiyang, Kraiczy, Judith, Gu, Wei, Perlov, Yakov, Beyaz, Semir, Wang, Timothy Cragin, Zhou, Qiao, Shivdasani, Ramesh Arjun (February 2025) Niche-driven phenotypic plasticity and cis-regulatory dynamics of a revised model for intestinal secretory differentiation. bioRxiv. ISSN 2692-8205 (Public Dataset)

Abstract

Enterocytes and four secretory cell types derive from stem cells located in intestinal crypts. Whereas secretory goblet and Paneth cells have long been considered distinct, we find high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of sibling enteroendocrine or tuft cells. Mouse and human goblet and Paneth cells express extraordinary fractions of selective antimicrobial genes, reflecting specific and variable gene responses to local niche signals. Wnt signaling retains few ATOH1+ secretory daughters in crypt bottoms, where an absence of BMP signaling potently induces Paneth features; those that move away from crypt bottoms acquire classic goblet properties. These post-mitotic cellular phenotypes and their underlying accessible cis-elements interconvert readily. Thus, goblet and Paneth properties represent alternative manifestations of a single versatile signal-responsive secretory cell. These findings reveal exquisite niche-dependent cell plasticity and the cis-regulatory dynamics of an updated unitarian model of the intestinal epithelial lineage.

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 > DNA, RNA structure, function, modification > cis-regulatory elements
bioinformatics > genomics and proteomics > cis regulatory variation
CSHL Authors:
Communities: CSHL labs > Beyaz lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 8 February 2025
Date Deposited: 03 Mar 2025 13:05
Last Modified: 03 Mar 2025 13:05
PMCID: PMC11839133
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/41803

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