Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors

作者：Laura Lukjanenko, S. Karaz, P. Stuelsatz, Uxia Gurriaran-Rodriguez, J. Michaud, Gabriele Dammone, F. Sizzano, O. Mashinchian, Sara Ancel, E. Migliavacca, Sophie Liot, Guillaume E. Jacot, S. Métairon, F. Raymond, P. Descombes, A. Palini, B. Chazaud, Michael A. Rudnicki, C. Bentzinger, J. Feige · 发表于：Cell Stem Cell · 年份：2019 · DOI：10.1016/j.stem.2018.12.014 · 被引用次数：289 · 研究领域：Biology、Medicine

Summary 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 demonstrate that this mechanism can be targeted to rejuvenate myogenesis.