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

被引：128

作者：

Frank-Bertoncelj, Mojca ^{[1
,2
]}

Trenkmann, Michelle ^{[1
,2
]}

Klein, Kerstin ^{[1
,2
]}

Karouzakis, Emmanuel

Rehrauer, Hubert ^{[3
,4
]}

Bratus, Anna ^{[3
,4
]}

Kolling, Christoph ^{[5
]}

Armaka, Maria ^{[6
]}

Filer, Andrew ^{[7
]}

Michel, Beat A. ^{[1
,2
]}

Gay, Renate E. ^{[1
,2
]}

Buckley, Christopher D. ^{[7
]}

Kollias, George ^{[6
,8
]}

Gay, Steffen ^{[1
,2
,9
]}

Ospelt, Caroline ^{[1
,2
,9
]}

机构：

[1] Univ Zurich, Ctr Expt Rheumatol, Wagistrasse 14, Zurich, Switzerland

[2] Univ Zurich Hosp, Ctr Expt Rheumatol, Wagistrasse 14, Zurich, Switzerland

[3] Univ Zurich, Funct Genom Ctr Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

[4] Swiss Fed Inst Technol, Funct Genom Ctr Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

[5] Schulthess Clin, Lengghalde 2, CH-8008 Zurich, Switzerland

[6] Biomed Sci Res Ctr Alexander Fleming, Div Immunol, 34,Fleming St, Attica, Greece

[7] Univ Birmingham, Queen Elizabeth Hosp, Inst Inflammat & Ageing IIA, Birmingham B15 2WB, England

[8] Univ Athens, Sch Med, Dept Expt Physiol, 75 Mikras Asias St, Athens, Greece

[9] Univ Zurich, Ctr Appl Biotechnol & Mol Med CABMM, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国惠康基金;

关键词：

LONG NONCODING RNA; HOX GENES; DNA METHYLATION; PALMOPLANTAR FIBROBLASTS; EROSIVE OSTEOARTHRITIS; HOMEOTIC GENE; EXPRESSION; CHROMATIN; HISTONE; SITE;

D O I：

10.1038/ncomms14852

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 65 条

[1] Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes [J].