Culture substrate stiffness impacts human myoblast contractility-dependent proliferation and nuclear envelope wrinkling.

Understanding how biophysical and biochemical microenvironmental cues together influence the regenerative activities of muscle stem cells and their progeny is crucial in strategizing remedies for pathological dysregulation of these cues in aging and disease. In this study, we investigated the cell-level influences of extracellular matrix (ECM) ligands and culture substrate stiffness on primary human myoblast contractility and proliferation within 16 h of plating and found that tethered fibronectin led to stronger stiffness-dependent responses compared to laminin and collagen. A proteome-wide analysis further uncovered cell metabolism, cytoskeletal and nuclear component regulation distinctions between cells cultured on soft and stiff substrates. Interestingly, we found that softer substrates increased the incidence of myoblasts with a wrinkled nucleus, and that the extent of wrinkling could predict Ki67 (also known as MKI67) expression. Nuclear wrinkling and Ki67 expression could be controlled by pharmacological manipulation of cellular contractility, offering a potential cellular mechanism. These results provide new insights into the regulation of human myoblast stiffness-dependent contractility response by ECM ligands and highlight a link between myoblast contractility and proliferation.

Decoding the forces that shape muscle stem cell function.

Skeletal muscle is a force-producing organ composed of muscle tissues, connective tissues, blood vessels, and nerves, all working in synergy to enable movement and provide support to the body. While robust biomechanical descriptions of skeletal muscle force production at the body or tissue level exist, little is known about force application on microstructures within the muscles, such as cells. Among various cell types, skeletal muscle stem cells reside in the muscle tissue environment and play a crucial role in driving the self-repair process when muscle damage occurs. Early evidence indicates that the fate and function of skeletal muscle stem cells are controlled by both biophysical and biochemical factors in their microenvironments, but much remains to accomplish in quantitatively describing the biophysical muscle stem cell microenvironment. This book chapter aims to review current knowledge on the influence of biophysical stresses and landscape properties on muscle stem cells in heath, aging, and diseases.

An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.

Many tissues harbor quiescent stem cells that are activated upon injury, subsequently proliferating and differentiating to repair tissue damage. Mechanisms by which stem cells sense injury and transition from quiescence to activation, however, remain largely unknown. Resident skeletal muscle stem cells (MuSCs) are essential orchestrators of muscle regeneration and repair. Here, with a combination of in vivo and ex vivo approaches, we show that quiescent MuSCs have elaborate, Rac GTPase-promoted cytoplasmic projections that respond to injury via the upregulation of Rho/ROCK signaling, facilitating projection retraction and driving downstream activation events. These early events involve rapid cytoskeletal rearrangements and occur independently of exogenous growth factors. This mechanism is conserved across a broad range of MuSC activation models, including injury, disease, and genetic loss of quiescence. Our results redefine MuSC activation and present a central mechanism by which quiescent stem cells initiate responses to injury.

[An independent observatory in Vendée on ST-elevated acute myocardial infarction (the OVISCA Register). A Departmental evaluation of demographic trends, mortality and delays before treatment]. / Observatoire Vendéen indépendant des syndromes Coronarien aigus avec sus-décalage du segment ST (Registre OVISCA). Évaluation départementale, évolution démographique, mortalité, délais de prise en charge.

AIM: Mortality from acute myocardial infarction has been falling during the past 30 years. The aim of the study was to evaluate the temporal trends of demographics, mortality rates, and time to treatment in patients admitted for acute ST elevation myocardial infarction (STEMI) in Vendée. PATIENTS AND METHODS: From 2008 to 2016, 1994 patients hospitalised in CHD Vendée for STEMI <48hours were included. Two groups were compared, 838 patients admitted between 2008 and 2011 (group 1), and 1156 admitted between 2013 and 2016 (group 2). RESULTS: Between the 2 periods, mean age was comparable (63.8 vs. 64.4 years), the gender ratio decreased (from 3.15 to 2.79 ; P=0.25). The mean duration of hospital stay was 0.8 day shorter (P=0.008). Treatment at discharge was optimum in 97.5% patients versus 92% (P<0.001). Left ventricular ejection fraction was comparable (50.6% vs. 50.2%). There was a non-significant trend to a decrease in hospital mortality (from 6.3% to 4.4%; p=0.12), and 6-month mortality (from 6.9% to 5.9%; P=0.51). There was a reduction in the use of emergency call-outs (74.9% to 68.9%; P<0.01), but an increase in direct presentations from 44% to 48.7% (P<0.05). The time before calling was comparable (2.5hours vs. 2.3hours; P=04.7). The "door-to-balloon" time decreased (0.71 vs. 0.55hour; P<0.001). The mean time between pain and angioplasty increased (5.7 vs. 6.8hours; P<0.05). CONCLUSIONS: In vendee, from 2011 to 2016, hospital and 6-month mortality of STEMI trend to decrease non-significantly. The door to balloon time decreased, although emergency call-out rates and delays did not. Considerable efforts are still required with respect to patient information and education. Our registry offers an excellent tool to improve practices, the aim being to ensure its integration in the CRAC-France PCI registry.