Mesenchymal Stromal Cells Are Required for Regeneration and Homeostatic Maintenance of Skeletal Muscle

被引：293

作者：

Wosczyna, Michael N. ^{[1
,2
]}

Konishi, Colin T. ^{[1
,2
]}

Carbajal, Edgar E. Perez ^{[1
,2
]}

Wang, Theodore T. ^{[1
,2
]}

Walsh, Rachel A. ^{[1
,2
]}

Gan, Qiang ^{[1
,2
]}

Wagner, Mark W. ^{[1
,2
]}

Rando, Thomas A. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Paul F Glenn Ctr Biol Aging, Stanford, CA 94305 USA

[3] Vet Affairs Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA 94304 USA

来源：

CELL REPORTS | 2019年 / 27卷 / 07期

关键词：

CONNECTIVE-TISSUE FIBROBLASTS; SATELLITE CELLS; FIBRO/ADIPOGENIC PROGENITORS; INJURY; RESIDENT; REPAIR; ADULT;

D O I：

10.1016/j.celrep.2019.04.074

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The necessity of mesenchymal stromal cells, called fibroadipogenic progenitors (FAPs), in skeletal muscle regeneration and maintenance remains unestablished. We report the generation of a PDGFR alpha(creER) knockin mouse model that provides a specific means of labeling and targeting FAPs. Depletion of FAPs using Cre-dependent diphtheria toxin expression results in loss of expansion of muscle stem cells (MuSCs) and CD45+ hematopoietic cells after injury and impaired skeletal muscle regeneration. Further-more, FAP-depleted mice under homeostatic conditions exhibit muscle atrophy and loss of MuSCs, revealing that FAPs are required for the maintenance of both skeletal muscle and the MuSC pool. We also report that local tamoxifen metabolite delivery to target CreER activity in a single muscle, removing potentially confounding systemic effects of ablating PDGFR alpha+ cells distantly, also causes muscle atrophy. These data establish a critical role of FAPs in skeletal muscle regeneration and maintenance.

引用

页码：2029 / +

页数：12

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