当前位置：
X-MOL 学术
›
Cell Stem Cell
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-01-24 , DOI: 10.1016/j.stem.2018.12.014 Laura Lukjanenko 1 , Sonia Karaz 2 , Pascal Stuelsatz 2 , Uxia Gurriaran-Rodriguez 3 , Joris Michaud 2 , Gabriele Dammone 2 , Federico Sizzano 2 , Omid Mashinchian 1 , Sara Ancel 1 , Eugenia Migliavacca 2 , Sophie Liot 4 , Guillaume Jacot 2 , Sylviane Metairon 2 , Frederic Raymond 2 , Patrick Descombes 2 , Alessio Palini 2 , Benedicte Chazaud 4 , Michael A Rudnicki 3 , C Florian Bentzinger 5 , Jerome N Feige 1
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-01-24 , DOI: 10.1016/j.stem.2018.12.014 Laura Lukjanenko 1 , Sonia Karaz 2 , Pascal Stuelsatz 2 , Uxia Gurriaran-Rodriguez 3 , Joris Michaud 2 , Gabriele Dammone 2 , Federico Sizzano 2 , Omid Mashinchian 1 , Sara Ancel 1 , Eugenia Migliavacca 2 , Sophie Liot 4 , Guillaume Jacot 2 , Sylviane Metairon 2 , Frederic Raymond 2 , Patrick Descombes 2 , Alessio Palini 2 , Benedicte Chazaud 4 , Michael A Rudnicki 3 , C Florian Bentzinger 5 , Jerome N Feige 1
Affiliation
|
Research on age-related regenerative failure of skeletal muscle has extensively focused on the phenotypes of muscle stem cells (MuSCs). In contrast, the impact of aging on regulatory cells in the MuSC niche remains largely unexplored. Here, we demonstrate that aging impairs the function of mouse fibro-adipogenic progenitors (FAPs) and thereby indirectly affects the myogenic potential of MuSCs. Using transcriptomic profiling, we identify WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as a FAP-derived matricellular signal that is lost during aging. WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling. Transplantation of young FAPs or systemic treatment with WISP1 restores the myogenic capacity of MuSCs in aged mice and rescues skeletal muscle regeneration. Our work establishes that loss of WISP1 from FAPs contributes to MuSC dysfunction in aged skeletal muscles and demonstrates that this mechanism can be targeted to rejuvenate myogenesis.
中文翻译：
衰老通过损害纤维成脂祖细胞的基质细胞WISP1分泌而破坏肌肉干细胞功能。
骨骼肌与年龄相关的再生衰竭的研究广泛地集中在肌肉干细胞（MuSCs）的表型上。相比之下，衰老对MuSC生态位中调控细胞的影响仍未发现。在这里，我们证明了衰老会损害小鼠纤维成脂祖细胞（FAP）的功能，从而间接影响MuSCs的成肌潜能。使用转录组分析，我们将WNT1诱导信号通路蛋白1（WISP1）识别为FAP衍生的基质细胞信号，该信号在衰老过程中丢失。WISP1是有效的肌肉再生所必需的，并通过Akt信号传导控制MuSC的扩增和不对称定型。年轻的FAP移植或WISP1的全身治疗可恢复老年小鼠MuSC的成肌能力，并拯救骨骼肌再生。
更新日期：2019-01-25
中文翻译：
衰老通过损害纤维成脂祖细胞的基质细胞WISP1分泌而破坏肌肉干细胞功能。
骨骼肌与年龄相关的再生衰竭的研究广泛地集中在肌肉干细胞（MuSCs）的表型上。相比之下，衰老对MuSC生态位中调控细胞的影响仍未发现。在这里，我们证明了衰老会损害小鼠纤维成脂祖细胞（FAP）的功能，从而间接影响MuSCs的成肌潜能。使用转录组分析，我们将WNT1诱导信号通路蛋白1（WISP1）识别为FAP衍生的基质细胞信号，该信号在衰老过程中丢失。WISP1是有效的肌肉再生所必需的，并通过Akt信号传导控制MuSC的扩增和不对称定型。年轻的FAP移植或WISP1的全身治疗可恢复老年小鼠MuSC的成肌能力，并拯救骨骼肌再生。
京公网安备 11010802027423号