Dissecting Fibroblast Heterogeneity in Health and Fibrotic Disease

Tanya J. Shaw, Emanuel Rognoni*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

49 Citations (Scopus)

Abstract

Purpose of Review: Fibroblasts, the major cell population in all connective tissues, are best known for their role in depositing and maintaining the extracellular matrix. Recently, numerous specialised functions have been discovered revealing unpredicted fibroblast heterogeneity. We will discuss this heterogeneity, from its origins in development to alterations in fibrotic disease conditions. Recent Findings: Advances in lineage tracing and single-cell transcriptional profiling techniques have revealed impressive diversity amongst fibroblasts in a range of organ systems including the skin, lung, kidney and heart. However, there are major challenges in assimilating the findings and understanding their functional significance. Certain fibroblast subsets can make specific contributions to healthy tissue functioning and to fibrotic disease processes; thus, therapeutic manipulation of particular subsets could be clinically beneficial. Summary: Here we propose that four key variables determine a fibroblast’s phenotype underpinning their enormous heterogeneity: tissue status, regional features, microenvironment and cell state. We review these in different organ systems, highlighting the importance of understanding the divergent fibroblast properties and underlying mechanisms in tissue fibrosis.

Original languageEnglish
Article number33
JournalCurrent Rheumatology Reports
Volume22
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • Cell heterogeneity
  • Fibroblast
  • Fibrosis
  • Myofibroblast
  • Single-cell transcriptomics
  • Tissue injury

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