Slow ‐Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

This article is protected by copyright. All rights reserved. Fiber‐type proportions are responsible for skeletal muscle properties including contractility, metabolism (glycolytic and oxidative), and fatigue resistance, as well as its susceptibility to disease conditions and its plasticity to respond to demands of exercise or disuse. The mechanism that restores the original muscle‐specific fiber‐type composition after a muscle regenerates from trauma or chemical insult is not well understood. Here we show that Sema3A ligand, which is secreted from resident myogenic stem satellite cells exclusively at the early‐differentiation phase (in a HGF/syndecan2, 4‐dependent manner), impacts slow‐fiber commitment through a signaling pathway from the cell‐membrane receptor (neuropilin2‐plexinA3) → myogenin (and MEF2D/HDAC7) → slow myosin heavy chain (MyHC). The detailed mechanistic connections between neuropilin2‐plexinA3, myogenin, and slow MyHC await further study. The model includes additional elements that Sema3A‐neuropilin2/plexinA3 and Sema3A‐neuropilin1/plexinA1, A2 coupling may enhance slow‐fiber formation by activating signals that inhibit fast‐myosin expression. At the subsequent growth phase, Sema3A expression returns to basal level and hence the motor innervation may be established on slow‐MyHC‐positive myotubes. The innervation contributes to fiber‐type maturation through a calcium/calcineurin signaling pathway, in synchrony with configura...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research