Dissecting Fibroblast Heterogeneity in Health and Fibrotic Disease

TY - JOUR

T1 - Dissecting Fibroblast Heterogeneity in Health and Fibrotic Disease

AU - Shaw, Tanya J.

AU - Rognoni, Emanuel

PY - 2020/8/1

Y1 - 2020/8/1

N2 - 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.

AB - 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.

KW - Cell heterogeneity

KW - Fibroblast

KW - Fibrosis

KW - Myofibroblast

KW - Single-cell transcriptomics

KW - Tissue injury

UR - http://www.scopus.com/inward/record.url?scp=85086701609&partnerID=8YFLogxK

U2 - 10.1007/s11926-020-00903-w

DO - 10.1007/s11926-020-00903-w

M3 - Review article

C2 - 32562113

AN - SCOPUS:85086701609

SN - 1523-3774

VL - 22

JO - Current Rheumatology Reports

JF - Current Rheumatology Reports

IS - 8

M1 - 33

ER -