SVEP1 is a Novel Marker of Activated Pre-determined Skeletal Muscle Satellite Cells

Abstract

In this study we explored the expression pattern of SVEP1, a novel cell adhesion molecule (CAM), in bona fide satellite cells and their immediate progeny. We show that SVEP1 is expressed in activated satellite cells prior to their determination to the myogenic lineage. SVEP1 was also expressed during early phases of myogenic differentiation through the initial stage of myoblast fusion and myotube formation. The expression of SVEP1 was shown by immunostaining two cell culture systems: freshly isolated myofibers and primary myoblasts. Pax7 was used to pinpoint satellite cells situated in their niche on myofibers, and activated satellite cells were determined based on BrdU incorporation (Pax7(+)/BrdU(+)cells). MyoD marked satellite cells fated to undergo myogenesis as well as proliferating and differentiating myoblasts. Differentiating myoblasts and myotubes were identified based on their sarcomeric myosin expression. We showed that SVEP1 was specifically expressed in pre-determined activated satellite cells (Pax7(+)/ BrdU(+) /MyoD(-)) accounting for about 24% of total satellite cells. On the other hand, SVEP1 expression was absent in quiescent satellite cells (Pax7(+)/BrdU(-)/MyoD(-)). Moreover, based on MyoD/sarcomeric myosin co-expression SVEP1 was shown to be expressed throughout the early phases of myogenesis up until myoblast fusion and myotube formation. A decline in SVEP1 expression occurred upon myotube maturation. We suggest SVEP1 as a potential biomarker for pre-fated satellite cells. The impact of this finding is that it may allow scrutinizing signals that affect differentiation commitment. Thus, holds a therapeutic potential for maladies that involve deregulated stem cell fate-decision.

Expression pattern of SVEP1 alternatively-spliced forms

“…SVEP1 expression was identified in skeletal tissues in vivo, mesenchymal stem cells (MSCs) derived from human, mouse and rat bone marrow, and in pre-osteoblastic cells (MBA-15) (Shur et al, 2006(Shur et al, , 2007. SVEP1 is also expressed by skeletal muscle-activated satellite cells (Shefer and Benayahu, 2010). SVEP1 protein expression was analyzed in a series of human and mouse breast cancer (BC) cell lines (GlaitSantar andBenayahu, 2011, 2012;Shur et al, 2007;Socher and Benayahu, 2008).…”

“…Previous studies demonstrated that the SVEP1 gene is expressed in skeletal tissues, in vivo and in vitro by mesenchymal stem cells (MSCs) derived from bone marrow (Shur et al, 2006) and by skeletal muscle activated stem cells (Shefer and Benayahu, 2010). In addition, we identified its expression in a series of human breast cancer (BC) cell lines.…”

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions

“…The platelet binding protein GspB (s6_14291) was shown to decline in transcript abundance in HL. Finally, the Symb6 library contains 40 transcripts encoding Svep1 (Sushi, von Willebrand factor type A, epidermal growth factor and pentraxin domain-containing protein 1), a novel cell adhesion molecule (Shefer and Benayahu, 2010). The levels of three transcripts encoding Svep1 were also reduced in the dark while two others were reduced in cells exposed to 24 h of HL in IMK + cas (Figure 5c).…”

Loss ofPim1Imposes a Hyperadhesive Phenotype on Endothelial Cells

“…Genes were selected 7 out of these 12 genes could be validated using qRT-PCR (Fig. 6A): the integrin family member integrin alpha 7 (Itga7), the junctional adhesion molecule 2 (Jam2), T-cadherin also known as cadherin 13 (Cdh13), a disintegrin and metalloproteinase [27]. The most significantly regulated genes also displaying the highest mRNA expression levels in Pim1 -/-cells were identified as Col6a3 (fold induction = 51.6; P<0.0001), and Cdh13 (fold induction = 81.9; P<0.0002) (Fig.…”