Monocyte Subsets With High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8.
Monocyte Subsets With High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8.
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DOI：
10.1002/jbmr.4165
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Thumbigere-Math V
中科院分区：
文献类型：
--
作者：
Das A;Wang X;Kang J;Coulter A;Shetty AC;Bachu M;Brooks SR;Dell'Orso S;Foster BL;Fan X;Ozato K;Somerman MJ;Thumbigere-Math V
破骨细胞是由单核细胞串联融合形成的骨吸收细胞。在小鼠和人类中，存在三种不同的单核细胞亚群；然而，尚不清楚是否所有这些亚群都显示出破骨细胞的潜能。在这里，我们表明在野生型小鼠中，与Ly6C−单核细胞相比，Ly6CHI和Ly6Cint单核细胞是OC形成的主要来源。它们的破骨潜能取决于信号受体表达的增加和预先建立的转录本的激活，以及在增强子活性和启动子变化中的从头获得。在缺乏IRF8转录因子的情况下，所有三个单核细胞亚群都被编程为显示更高的破骨细胞潜能。早期发育阶段开始的NFATc1核转位增强和转录和表观遗传学变化导致了IRF8缺陷小鼠破骨细胞生成的增加。总之，我们的研究为调控OC分化的转录因子和活性顺式调节元件提供了新的见解。
Osteoclasts (OCs) are bone resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C− monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of pre-established transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of IRF8, a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8 deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation.
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DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
DOI：
10.4049/jimmunol.1501466
发表时间：
2016-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fang C;Qiao Y;Mun SH;Lee MJ;Murata K;Bae S;Zhao B;Park-Min KH;Ivashkiv LB
通讯作者：
Ivashkiv LB
DOI：
10.4049/jimmunol.1001950
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Feng J;Wang H;Shin DM;Masiuk M;Qi CF;Morse HC 3rd
通讯作者：
Morse HC 3rd
影响因子：
5.8
作者：
Carey, Heather A.;Hildreth, Blake E., III;Sharma, Sudarshana M.
通讯作者：
Sharma, Sudarshana M.
影响因子：
20.3
作者：
Becker, Amy M.;Michael, Drew G.;Bhattacharya, Deepta
通讯作者：
Bhattacharya, Deepta