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Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions


Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C

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.

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Published
March, 2017

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    C15410196
    H3K27ac Antibody
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    C15410195
    H3K27me3 Antibody
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    C15410003-50
    H3K4me3 Antibody
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    C01010051
    iDeal ChIP-seq kit for Histones
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    C05010012
    MicroPlex Library Preparation Kit v2 (12 indexes)

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