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Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity

Rossi, CA; Pozzobon, M; Ditadi, A; Archacka, K; Gastaldello, A; Sanna, M; Franzin, C; ... De Coppi, P; + view all (2010) Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity. PLOS ONE , 5 (1) , Article e8523. 10.1371/journal.pone.0008523. Green open access

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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 (similar to 75%) and the high proliferative clones (HPC), present instead in minor amount (similar to 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 (Delta Psi(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.

Type: Article
Title: Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0008523
Publisher version: http://dx.doi.org/10.1371/journal.pone.0008523
Language: English
Additional information: © 2010 Rossi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. C.A.R. was supported by Telethon (Grant GGP07216). K.A. by FEBS Collaborative Experimental Scholarship for Central & Eastern Europe, A.G. by English-Italian Cultural Association il Circolo. This work was supported by Telethon grant (GGP07216) and Fondazione Citta' della Speranza grant (04/02), CRF (University of London), RVC internal funds for supporting the research activity in the M.C. laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: REGENERATING SKELETAL-MUSCLE, OIL RED-O, STEM-CELLS, SELF-RENEWAL, ADIPOGENIC DIFFERENTIATION, DYSTROPHIC MUSCLE, IN-VITRO, EXPRESSION, POPULATIONS, QUIESCENT
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/121075
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