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Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
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Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
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Journal Article
Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
2017
Overview
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.
Arthritis affects different joints variably despite systemic inflammatory cues. Here the authors show anatomical differences in the transcriptome, epigenome and function of synovial fibroblasts that might affect susceptibility to site-specific joint diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/21
/ 38/109
/ 38/15
/ 38/88
/ 38/91
/ 64/110
/ 64/60
/ 82/80
/ Animals
/ Arthritis, Rheumatoid - genetics
/ Arthritis, Rheumatoid - metabolism
/ Arthritis, Rheumatoid - pathology
/ Disease
/ Genomics
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Knee
/ Science
/ Shoulder
/ Skin
/ Synovial Membrane - cytology
