Skeletal muscle satellite cells and adult myogenesis

Abstract

Research focusing on the canonical adult myogenic progenitor, the skeletal muscle satellite cell, is still an ever-growing field 46 years from their initial description. Recent publications revealed numerous new aspects of satellite cell biology, starting from their developmental life to their role as the principal self-renewing myogenic stem cell in adult skeletal muscle and finally their loss during aging. The myogenic potential of satellite cells is under the molecular control of specific paired-box and bHLH transcription factors whose tightly orchestrated balance accounts for an effective skeletal muscle regeneration. New reports also demonstrate satellite cells relationships with blood vessels and the high myogenic potential of stem cell subsets related to both lineages.

Figure 1. Schematic representation of adult myogenesis

Quiescent skeletal muscle satellite cell can become activated following stimuli originating from their associated fiber or from the micro-environment. Their proliferating progeny, the skeletal myoblasts, express the paired-box transcriptions factors Pax7 and Pax3, as well as the myogenic regulatory factors Myf5 and MyoD. Once committed to differentiation, myoblasts stop cycling and loose expression of Pax7, Pax3 and Myf5. Differentiating myogenin+ve myocytes will then align and fuse to form multinucleated myofibers. MRF4 is further required for hypertrophy of the new fibers.

Figure 2. Satellite cell hierarchy and self-renewal

During regeneration, satellite stem (Myf5YFP-ve) cells can asymmetrically divide and give rise to a self-renewing daughter (blue arrow) and a committed (Myf5YFP+ve) daughter. Committed cells become activated, leave the sub-laminar niche and proliferate. Myf5+ve cycling myoblasts mainly differentiate and contribute to new fiber formation., Some Myf5+ve myoblasts can also downregulate MyoD and return to quiescence (red arrow), thus replenishing the niche. Myf5-ve stem cells arealso postulated as being able to give rise to uncommitted progenitors which will participate in regeneration of the tissue (grey arrow).