Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
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DOI：
10.1038/s41467-018-03876-8
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发表时间：
2018-04-18
影响因子：
16.6
通讯作者：
Blau HM
中科院分区：
文献类型：
--
作者：
Sampath SC;Sampath SC;Ho ATV;Corbel SY;Millstone JD;Lamb J;Walker J;Kinzel B;Schmedt C;Blau HM
骨骼肌中干细胞静止和增殖之间的平衡受到严格控制，但在各种疾病状态下受到干扰。尽管在鉴定干细胞增殖的激活剂方面取得了进展，但负责静止诱导的生态位因子仍不清楚。在这里，我们报告了一个在体内成像为基础的屏幕，其中确定肿瘤抑制素M（OSM），白细胞介素-6家族的细胞因子的成员，作为一个强大的诱导剂的肌肉干细胞（MuSC，卫星细胞）静止。OSM由肌纤维产生，诱导可逆的MuSC细胞周期退出，并维持干细胞再生能力，如通过连续移植所判断的。卫星细胞中的条件性OSM受体缺失导致干细胞耗竭和损伤后再生受损。这些结果鉴定了抑瘤素M作为负责静止诱导的分泌型小生境因子，并且首次建立了固体器官干细胞中静止诱导、干性和移植潜力之间的直接联系。介导肌肉干细胞静止的因素尚不清楚。作者表明，Oncostatin M由骨骼肌产生，抑制干细胞增殖，并且其在肌肉中的缺失导致小鼠损伤后干细胞耗竭和肌肉再生受损。
The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identifies Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent inducer of muscle stem cell (MuSC, satellite cell) quiescence. OSM is produced by muscle fibers, induces reversible MuSC cell cycle exit, and maintains stem cell regenerative capacity as judged by serial transplantation. Conditional OSM receptor deletion in satellite cells leads to stem cell depletion and impaired regeneration following injury. These results identify Oncostatin M as a secreted niche factor responsible for quiescence induction, and for the first time establish a direct connection between induction of quiescence, stemness, and transplantation potential in solid organ stem cells. The factors that mediate quiescence of muscle stem cells are unknown. The authors show that Oncostatin M is produced by skeletal muscle, suppresses stem cell proliferation, and that its deletion in muscle results in stem cell depletion and impaired muscle regeneration following injury in mice.
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DOI：
10.1242/dev.100842
发表时间：
2014-04
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chakkalakal JV;Christensen J;Xiang W;Tierney MT;Boscolo FS;Sacco A;Brack AS
通讯作者：
Brack AS
DOI：
10.1073/pnas.0914019107
发表时间：
2010-02-23
影响因子：
11.1
作者：
Gonzalez, Rodolfo;Jennings, Lori L.;Lesley, Scott A.
通讯作者：
Lesley, Scott A.
影响因子：
16.2
作者：
Delgado, Ana C.;Ferron, Sacri R.;Farinas, Isabel
通讯作者：
Farinas, Isabel
DOI：
10.1073/pnas.2637010100
发表时间：
2004-01-06
影响因子：
11.1
作者：
Cao, YA;Wagers, AJ;Contag, CH
通讯作者：
Contag, CH
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM