Faculty, Staff and Student Publications

Publication Date

4-11-2024

Journal

Cell

Abstract

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

Keywords

Animals, Humans, Mice, Colitis, Colitis, Ulcerative, Fibroblasts, In Situ Hybridization, Fluorescence, Inflammation, Cell Communication, Gastrointestinal Tract

DOI

10.1016/j.cell.2024.03.013

PMID

38569542

PMCID

PMC11017707

PubMedCentral® Posted Date

4-11-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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