title: Autonomous Extracellular Matrix Remodeling Controls a Progressive Adaptation in Muscle Stem Cell Regenerative Capacity during Development.
abstract: Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair.
authors.affiliation: Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA; Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Matthew Timothy
authors.initials: MT
authors.lastname: Tierney
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA; Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0685, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Gromova
authors.affiliation: Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA; Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Francesca Boscolo
authors.initials: FB
authors.lastname: Sesillo
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sala
authors.affiliation: Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Spenlé
authors.affiliation: Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Gertraud
authors.initials: G
authors.lastname: Orend
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: asacco@sbpdiscovery.org.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sacco
mesh_terms: D000818:Animals; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005109:Extracellular Matrix / Q000378:metabolism*; D005333:Fetus; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI; D005353:Fibronectins; D019063:Tenascin; D008156:Luciferases