Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs

Yang, Xiaochun, Steffani, Marcella, Nadella, Sandeep, Sheppard, Dean, Rieder, Florian, Rinkevich, Yuval, Kramann, Rafael, Tuveson, David A, Schwabe, Robert F (July 2026) Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs. JCI insight, 11 (13). ISSN 2379-3708

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Abstract

As the principal ECM-producing cell type, fibroblasts are essential regulators of tissue architecture and function in development, homeostasis, and disease. While their disease-promoting functions in fibrosis have long been the center of attention, it is increasingly recognized that fibroblasts exert critical homeostatic roles across organs, acting as sentinels that regulate the function, proliferation, and recruitment of epithelial, endothelial and immune cells in health and disease. Here, we will review the roles of fibroblasts and fibroblast-like cells in tissue maintenance, physiological wound healing, regeneration, maladaptive fibrosis, and cancer across major organs, including the skin, lung, liver, intestine, and kidney, and highlight organ-specific and shared populations and functions. We will discuss the role of PI16+ and COL15A1+ universal fibroblasts, organ-specific fibroblasts, and pericyte and pericyte-like stellate cells as cellular sources for the majority of CTHRC1+ activated fibroblasts and αSMA+ or LRRC15+ myofibroblasts and highlight the functions of specialized subpopulations, such as inflammatory fibroblasts, antigen-presenting fibroblasts, and fibroblast-like cells, including mesothelial and smooth muscle cells. A refined understanding of fibroblast heterogeneity holds promise for novel therapeutic concepts, aimed at targeting pathogenic subpopulations while preserving or enhancing homeostatic functions.

Item Type: Paper
Subjects: diseases & disorders
diseases & disorders > neoplasms
CSHL Authors:
Communities: CSHL labs > Tuveson lab
CSHL Cancer Center Program
CSHL Cancer Center Program > Cellular Communication in Cancer Program
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 8 July 2026
Date Deposited: 10 Jul 2026 12:17
Last Modified: 10 Jul 2026 12:17
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42267

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