Autonomous Extracellular Matrix Remodeling Controls a Progressive Adaptation in Muscle Stem Cell Regenerative Capacity during Development

• DOI: 10.1016/j.celrep.2016.01.072
• Publication Date: 2016-02-20T07:07:46Z
• Authors: Matthew Timothy T...; Anastasia Gromova; Francesca Boscolo...; David Sala; Caroline Spenlé; Gertraud Orend; Alessandra Sacco
• Keywords: Medical Physiology; Regenerative Medicine; Inbred C57BL; Muscle Development; Transgenic; Myoblasts; Mice; Stem Cell Research - Nonembryonic - Human; Genes, Reporter; Mice, Inbred NOD; Developmental; Biology (General); Luciferases; 0303 health sciences; Gene Expression Regulation, Developmental; Tenascin; Skeletal; Biological Sciences; Extracellular Matrix; Biological sciences; Embryo; Muscle; Stem Cell Research - Nonembryonic - Non-Human; Development of treatments and therapeutic interventions; Signal Transduction; 570; QH301-705.5; 1.1 Normal biological development and functioning; Myoblasts, Skeletal; Mice, Transgenic; 612; Collagen Type VI; Article; 03 medical and health sciences; Fetus; Underpinning research; Animals; Muscle, Skeletal; Reporter; Wound Healing; 5.2 Cellular and gene therapies; Mammalian; Stem Cell Research; Embryo, Mammalian; Fibronectins; Mice, Inbred C57BL; Gene Expression Regulation; Genes; Musculoskeletal; Inbred NOD; Biochemistry and Cell Biology; Stem Cell Transplantation

Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated poorly understood. Here, we show that fetal MuSCs resist progenitor specification and altered division dynamics, intrinsic features are progressively lost postnatally. After transplantation, expand more efficiently contribute muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between growth cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed MuSCs, including tenascin-C, fibronectin, collagen VI. Loss-of-function experiments confirmed essential stage-specific role regulating MuSC function. Finally, fetal-derived paracrine factors were able enhance adult regenerative potential. Together, these findings demonstrate change the way which they remodel microenvironment direct support unique demands development or