title: Clonal characterization of rat muscle satellite cells: proliferation, metabolism and differentiation define an intrinsic heterogeneity.
abstract: Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB) muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC) present in major proportion (approximately 75%) and the high proliferative clones (HPC), present instead in minor amount (approximately 25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (DeltaPsi(m)), ATP balance and Reactive Oxygen Species (ROS) generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described.
authors.affiliation: Stem Cell Processing Laboratory, Department of Pediatrics, University of Padua, Padova, Italy.
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Rossi
authors.forename: Michela
authors.initials: M
authors.lastname: Pozzobon
authors.forename: Andrea
authors.initials: A
authors.lastname: Ditadi
authors.forename: Karolina
authors.initials: K
authors.lastname: Archacka
authors.forename: Annalisa
authors.initials: A
authors.lastname: Gastaldello
authors.forename: Marta
authors.initials: M
authors.lastname: Sanna
authors.forename: Chiara
authors.initials: C
authors.lastname: Franzin
authors.forename: Alberto
authors.initials: A
authors.lastname: Malerba
authors.forename: Gabriella
authors.initials: G
authors.lastname: Milan
authors.forename: Mara
authors.initials: M
authors.lastname: Cananzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Schiaffino
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Campanella
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate