Dynamics of skeletal muscle-resident stem cells during myogenesis in fibrodysplasia ossificans progressiva.
Dynamics of skeletal muscle-resident stem cells during myogenesis in fibrodysplasia ossificans progressiva.
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DOI：
10.1038/s41536-021-00201-8
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发表时间：
2022-01-14
影响因子：
7.2
通讯作者：
Mourkioti F
中科院分区：
文献类型：
--
作者：
Stanley A;Tichy ED;Kocan J;Roberts DW;Shore EM;Mourkioti F
进行性骨化纤维发育不良（FOP）是一种罕见的遗传性疾病，在骨骼肌等组织内形成骨骼外（异位）骨，通常是对损伤的反应。BMP I型受体ACVR1/ALK2的突变通过增加BMP通路信号导致FOP。与对骨组织在FOP中不适当形成的了解越来越多相反，关于成人患病肌肉的再生能力仍有很多未知。利用可诱导的ACVR1R206H敲入小鼠，我们发现损伤的ACVR1R206H /+骨骼肌组织再生不良。我们证明，虽然两种干细胞群体，肌肉干细胞（MuSCs）和纤维/脂肪源性祖细胞（FAPs）在损伤后具有相似的增殖率，但突变MuSCs的分化潜力受到损害。尽管musc特异性缺失ACVR1R206H突变不会改变体内骨骼肌的再生潜能，但ACVR1R206H /+ musc会形成不发达的纤维，在体外无法融合。我们进一步确定来自Acvr1R206H/+小鼠的FAPs在体外抑制musc介导的Acvr1R206H/+肌管的形成。这些结果确定了ACVR1R206H在骨骼肌再生过程中通过组织内干细胞的不当相互作用，在FOP的肌肉发生中发挥了以前未被认识到的作用。
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease in which extraskeletal (heterotopic) bone forms within tissues such as skeletal muscles, often in response to injury. Mutations in the BMP type I receptor ACVR1/ALK2 cause FOP by increasing BMP pathway signaling. In contrast to the growing understanding of the inappropriate formation of bone tissue within the muscle in FOP, much is still unknown about the regenerative capacity of adult diseased muscles. Utilizing an inducible ACVR1R206H knock-in mouse, we found that injured Acvr1R206H/+ skeletal muscle tissue regenerates poorly. We demonstrated that while two resident stem cell populations, muscle stem cells (MuSCs) and fibro/adipogenic progenitors (FAPs), have similar proliferation rates after injury, the differentiation potential of mutant MuSCs is compromised. Although MuSC-specific deletion of the ACVR1R206H mutation does not alter the regenerative potential of skeletal muscles in vivo, Acvr1R206H/+ MuSCs form underdeveloped fibers that fail to fuse in vitro. We further determined that FAPs from Acvr1R206H/+ mice repress the MuSC-mediated formation of Acvr1R206H/+ myotubes in vitro. These results identify a previously unrecognized role for ACVR1R206H in myogenesis in FOP, via improper interaction of tissue-resident stem cells during skeletal muscle regeneration.
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影响因子：
12.4
作者：
通讯作者：
--
DOI：
10.1002/jbmr.2820
发表时间：
2016-09
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chakkalakal SA;Uchibe K;Convente MR;Zhang D;Economides AN;Kaplan FS;Pacifici M;Iwamoto M;Shore EM
通讯作者：
Shore EM
影响因子：
--
作者：
Friedrichs M;Wirsdöerfer F;Flohé SB;Schneider S;Wuelling M;Vortkamp A
通讯作者：
Vortkamp A
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
4.1
作者：
Loebel, Claudia;Czekanska, Ewa M.;Stoddart, Martin J.
通讯作者：
Stoddart, Martin J.