Clonal characterization of rat muscle satellite cells: Proliferation, metabolism and differentiation define an intrinsic heterogeneity

Carlo A. Rossi, Michela Pozzobon, Andrea Ditadi, Karolina Archacka, Annalisa Gastaldello, Marta Sanna, Chiara Franzin, Alberto Malerba, Gabriella Milan, Mara Cananzi, Stefano Schiaffino, Michelangelo Campanella, Roberto Vettor, Paolo De Coppi

Research output: Contribution to journalArticle

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 (-75%) and the high proliferative clones (HPC), present instead in minor amount (-25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if cocultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (Δψm), 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.

Original languageEnglish
Article numbere8523
JournalPLoS One
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Rossi, C. A., Pozzobon, M., Ditadi, A., Archacka, K., Gastaldello, A., Sanna, M., Franzin, C., Malerba, A., Milan, G., Cananzi, M., Schiaffino, S., Campanella, M., Vettor, R., & De Coppi, P. (2010). Clonal characterization of rat muscle satellite cells: Proliferation, metabolism and differentiation define an intrinsic heterogeneity. PLoS One, 5(1), [e8523]. https://doi.org/10.1371/journal.pone.0008523