Fibroblast heterogeneity: implications for human disease

Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial locat...

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Veröffentlicht in:The Journal of clinical investigation 2018-01, Vol.128 (1), p.26-35
Hauptverfasser: Lynch, Magnus D, Watt, Fiona M
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Watt, Fiona M
description Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.
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source MEDLINE; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects Aging
Animals
Arthritis
Biomedical research
Cancer
Collagen
Connective tissue
Dermis
Dermis - metabolism
Dermis - pathology
Disease
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Extracellular matrix
Fibroblasts
Fibroblasts - classification
Fibroblasts - metabolism
Fibroblasts - pathology
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Review Series
Rodents
Skin
Skin Neoplasms - classification
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Specialization
Therapeutic applications
Transcription
Transcription, Genetic
Wound healing
title Fibroblast heterogeneity: implications for human disease
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