Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal

Abstract

A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy.

A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression

“…Skeletal muscle regenerative capacity is partly dictated by their ability to balance the use of stem cells for normal or exercise-induced growth and for repair with the need to preserve a pool of quiescent stem cells acting as a reservoir for future needs. The MuSC niche, composed of extra-cellular matrix and non-myogenic cells (Rayagiri et al, 2018;Wosczyna and Rando, 2018), Figure 7G). Therefore, the combined activities of the primary cilium and Hh signalling provide an exquisite mechanism to control MuSC cell cycle progression and couple it to cell fate decision.…”

Identification of biomarkers indicative of functional skeletal stem cells

“…Knockdown of CD49f reduces differentiation potential of SSCs . Furthermore, CD49f plays an important role in the self‐renewal of PSCs, skeletal muscle stem cells, glioblastoma and breast cancer stem cells; its expression has been identified in 35 populations of stem cells . Flow cytometry data indicate that although close to 100% of cells were CD29‐positive and CD105‐positive during all 8 passages, only about 70% of PSC‐SSCs were CD49f‐positive at passage 3, and its expression decreased in subsequent passages and in cells that lost potential for proliferation and differentiation.…”

Single cell dynamics of embryonic muscle progenitor cells in zebrafish

“…First, the ECM might be an integral part of the niche that maintains the self-renewing property of MPCs. Recent work has implicated many ECM components, including fibronectin, tenascin-C, laminins and collagens, as critical niche factors that modulate satellite cell function (Bentzinger et al, 2013b;Fry et al, 2017;Rayagiri et al, 2018;Tierney et al, 2016;Urciuolo et al, 2013). In particular, it has been shown that collagen V produced by adult muscle satellite cells is an essential component of the quiescent niche, as deletion of the Col5a1 gene results in depletion of the stem cell pool (Baghdadi et al, 2018).…”

“…Quiescent satellite cells often display a bipolar morphology and reside beneath the basal lamina on the surface of the myofiber (Scharner and Zammit, 2011;Webster et al, 2016). The extracellular matrix (ECM) surrounding the satellite cell constitutes its niche and has been implicated in the regulation of satellite cell behavior (Baghdadi et al, 2018;Bentzinger et al, 2013b;Fry et al, 2017;Rayagiri et al, 2018;Tierney et al, 2016;Urciuolo et al, 2013). Upon muscle injury, 'activated' satellite cells undergo proliferation and initiate the myogenic program.…”