Molecular Mechanisms Implicated in Myogenic Differentiation of Human Alveolar Mucosa-Derived Cells

Abstract

Different approaches to skeletal muscle regeneration using progenitor cells are extensively studied as strategies for the treatment of muscle tissue pathologies. Recently, it was discovered that anatomically localized alveolar mucosa multipotent mesenchymal stromal cells (AMCs) are characterized by myogenic potential and high feasibility for muscle tissue recovery and regeneration. Although the resulting multinuclear myotubes express skeletal muscle-specific markers (skeletal myosin, actin, myogenin, and MyoD1), the exact molecular mechanism controlling myogenic differentiation of AMCs is still unclear and poorly scrutinized. In this research, we used a combination of large-scale transcriptome analysis and a bioinformatics approach to investigate molecular pathways and crucial nodes responsible for myogenic differentiation. We studied differentiation of AMC cells in 2D and 3D culture conditions and found core genes with significant expression changes during differentiation and compared them with skeletal muscle-derived stromal cells (SMCs). It appeared that differentiation of AMCs in 3D is significantly different from that in 2D. Moreover, differentiation of AMCs in 2D is closer to differentiation of SMCs in 2D than to AMCs in 3D. Unique properties of AMC differentiation in 3D may be attributed to a significant inhibition of the component of the PDGFRβ signaling pathway responsible for ruffle organization.