Fibroblasts: Origins, definitions, and functions in health and disease

Maksim V Plikus; Xiaojie Wang; Sarthak Sinha; Elvira Forte; Sean M Thompson; Erica L Herzog; Ryan R Driskell; Nadia Rosenthal; Jeff Biernaskie; Valerie Horsley

doi:10.1016/j.cell.2021.06.024

Fibroblasts: Origins, definitions, and functions in health and disease

Cell. 2021 Jul 22;184(15):3852-3872. doi: 10.1016/j.cell.2021.06.024.

Authors

Affiliations

¹ Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: plikus@uci.edu.
² Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA.
³ Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
⁴ The Jackson Laboratory, Bar Harbor, ME 04609, USA; National Heart and Lung Institute, Imperial College London, London SW7 2BX, UK.
⁵ School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
⁶ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: erica.herzog@yale.edu.
⁷ School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA; Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA. Electronic address: ryan.driskell@wsu.edu.
⁸ The Jackson Laboratory, Bar Harbor, ME 04609, USA; National Heart and Lung Institute, Imperial College London, London SW7 2BX, UK. Electronic address: nadia.rosenthal@jax.org.
⁹ Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: jeff.biernaskie@ucalgary.ca.
¹⁰ Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: valerie.horsley@yale.edu.

Abstract

Fibroblasts are diverse mesenchymal cells that participate in tissue homeostasis and disease by producing complex extracellular matrix and creating signaling niches through biophysical and biochemical cues. Transcriptionally and functionally heterogeneous across and within organs, fibroblasts encode regional positional information and maintain distinct cellular progeny. We summarize their development, lineages, functions, and contributions to fibrosis in four fibroblast-rich organs: skin, lung, skeletal muscle, and heart. We propose that fibroblasts are uniquely poised for tissue repair by easily reentering the cell cycle and exhibiting a reversible plasticity in phenotype and cell fate. These properties, when activated aberrantly, drive fibrotic disorders in humans.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Cell Lineage
Disease*
Fibroblasts / metabolism*
Health*
Humans
Molecular Targeted Therapy
Signal Transduction

Abstract

Publication types

MeSH terms

Grants and funding