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Fibroblast heterogeneity: implications for human disease

Authors :
Lynch, Magnus D.
Watt, Fiona M.
Source :
Journal of Clinical Investigation. January, 2018, Vol. 128 Issue 1, p26, 10 p.
Publication Year :
2018

Abstract

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.<br />Introduction A paradigm of the metazoan body plan is the combination of epithelial and mesenchymal elements into structured three-dimensional organs. Fibroblasts are cells that synthesize and integrate structural proteins such [...]

Details

Language :
English
ISSN :
00219738
Volume :
128
Issue :
1
Database :
Gale General OneFile
Journal :
Journal of Clinical Investigation
Publication Type :
Academic Journal
Accession number :
edsgcl.523063004
Full Text :
https://doi.org/10.1172/JCI93555.