Myogenic Potential of Canine Craniofacial Satellite Cells

Abstract

The skeletal fibers have different embryological origin; the extraocular and jaw-closer muscles develop from prechordal mesoderm while the limb and trunk muscles from somites. These different origins characterize also the adult muscle stem cells, known as satellite cells (SCs) and responsible for the fiber growth and regeneration. The physiological properties of presomitic SCs and their epigenetics are poorly studied despite their peculiar characteristics to preserve muscle integrity during chronic muscle degeneration. Here, we isolated SCs from canine somitic [somite-derived muscle (SDM): vastus lateralis, rectus abdominis, gluteus superficialis, biceps femoris, psoas] and presomitic [pre-somite-derived muscle (PSDM): lateral rectus, temporalis, and retractor bulbi] muscles as myogenic progenitor cells from young and old animals. In addition, SDM and PSDM-SCs were obtained also from golden retrievers affected by muscular dystrophy (GRMD). We characterized the lifespan, the myogenic potential and functions, and oxidative stress of both somitic and presomitic SCs with the aim to reveal differences with aging and between healthy and dystrophic animals. The different proliferation rate was consistent with higher telomerase activity in PSDM-SCs compared to SDM-SCs, although restricted at early passages. SDM-SCs express early (Pax7, MyoD) and late (myosin heavy chain, myogenin) myogenic markers differently from PSDM-SCs resulting in a more efficient and faster cell differentiation. Taken together, our results showed that PSDM-SCs elicit a stronger stem cell phenotype compared to SDM ones. Finally, myomiR expression profile reveals a unique epigenetic signature in GRMD SCs and miR-206, highly expressed in dystrophic SCs, seems to play a critical role in muscle degeneration. Thus, miR-206 could represent a potential target for novel therapeutic approaches.

The miR-206/133b cluster is dispensable for development, survival and regeneration of skeletal muscle

“…The normal expression of Pax7 in isolated miR-206/133b mutant satellite cells and the normal differentiation of mutant satellite cells to myotubes in vitro do not argue for an important role of miR-206 in Pax7 expression. These results are in contrast to previous publications mostly relying on the inhibition of miR-206 by anti-miRs [ 16 ], overexpression of miR-206 [ 15 , 36 ], or by correlation of expression profiles [ 37 , 38 ]. It seems possible that previous anti-miR approaches were biased by off-target effects or affected expression of miR-1, which can also suppress Pax7.…”

MicroRNAs modulated by local mIGF-1 expression in mdx dystrophic mice

“…On the contrary, McCarthy et al ( 2007 ) proposed that increased miR-206 expression may contribute to the chronic pathology of mdx diaphragm. In addition, miR-206 seems to be primarily involved in satellite cell impairment of dystrophic dogs, although its precise role needs to be elucidated (La Rovere et al, 2014 ). The apparent discrepancy among these studies and our findings can be justified considering that the up-regulation of miR-206 in the diaphragm of mdx/mIGF-1 might be related to its specific function in muscle differentiation instead in muscle pathology.…”

Craniofacial Muscle Development

“…In a recent study, canine craniofacial muscle satellite cells exhibited more efficient and faster differentiation and a stronger stem cell phenotype compared to somite-derived satellite cells (La Rovere et al, 2014). In contrast, satellite cells derived from mouse masseter muscle were able to regenerate muscle in a trunk muscle injury model as well as trunk-derived satellite cells (Harel et al, 2009;Ono et al, 2010).…”