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Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation.
- Source :
-
Cancer cell [Cancer Cell] 2024 Sep 17. Date of Electronic Publication: 2024 Sep 17. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Fibroblasts, known for their functional diversity, play crucial roles in inflammation and cancer. In this study, we conduct comprehensive single-cell RNA sequencing analyses on fibroblast cells from 517 human samples, spanning 11 tissue types and diverse pathological states. We identify distinct fibroblast subpopulations with universal and tissue-specific characteristics. Pathological conditions lead to significant shifts in fibroblast compositions, including the expansion of immune-modulating fibroblasts during inflammation and tissue-remodeling myofibroblasts in cancer. Within the myofibroblast category, we identify four transcriptionally distinct subpopulations originating from different developmental origins, with LRRC15 <superscript>+</superscript> myofibroblasts displaying terminally differentiated features. Both LRRC15 <superscript>+</superscript> and MMP1 <superscript>+</superscript> myofibroblasts demonstrate pro-tumor potential that contribute to the immune-excluded and immune-suppressive tumor microenvironments (TMEs), whereas PI16 <superscript>+</superscript> fibroblasts show potential anti-tumor functions in adjacent non-cancerous regions. Fibroblast-subtype compositions define patient subtypes with distinct clinical outcomes. This study advances our understanding of fibroblast biology and suggests potential therapeutic strategies for targeting specific fibroblast subsets in cancer treatment.<br />Competing Interests: Declaration of interests Z.Z. is a founder of Analytical Bioscience and also serves on the Advisory Board of Cell.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1878-3686
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 39303725
- Full Text :
- https://doi.org/10.1016/j.ccell.2024.08.020