The Path from Pluripotency to Skeletal Muscle: Developmental Myogenesis Guides the Way

Abstract

Following cues from mouse embryogenesis, Chal et al. (2015) identified key regulators of skeletal myogenesis from mouse and human pluripotent stem cells. Emerging myogenic progenitors were specified to form multinucleated fibers that enabled development of quiescent, satellite cell-like progenitors and a model for Duchenne Muscular Dystrophy.

Figure 1. Developmental Myogenesis Guides In Vitro Differentiation

(A) Timeline of skeletal myogenesis from E9.5–E16 mouse embryo. Left to right: images depict a mid-sagittal cross section of a mouse embryo during development and longitudinal sections of three somites. The somites give rise to the dermomyotome/myotome and migratory muscle progenitor cells that seed the limbs and mature to multinucleated fibers. Arrows indicate specific regions in the developing embryo (black). (B) Micro dissections of tissue regions between the first somite (S1) and tail bud were collected and profiled to aid in the identification of novel targets to drive in vitro myogenesis of mouse embryonic stem cells (mESCs). Not determined refers to the lack of profiling of the myotome and muscle fibers in this work. (C) The corresponding in vitro cells differentiated from mESCs using developmentally identified growth factors and small molecules are shown. Green nuclei indicate that Chal et al. utilized a reporter to monitor differentiation efficiency at each stage. pPSM, posterior presomitic mesoderm; aPSM, anterior presomitic mesoderm; S1, newly formed somite; DM, dermomyotome; M, myotome; LB, limb bud.