Biology subjects

Sebille, S.

Publications and source records attributed to Sebille, S..

4 recordsLinked to original sources

bioRxiv2024

DMD Human iPSC-derived skeletal muscle cells recapitulate selective calcium dysregulation pathways.

This study investigates the functional characteristics of induced pluripotent stem cell-derived muscle cells (hiPSC-skMCs) from Duchenne muscular dystrophy (DMD) patients, focusing on their regulation of intracellular calcium concentration. DMD, a progressive muscle degenerative disease, arises from mutations in the dystrophin gene and is characterized by elevated intracellular calcium levels, exacerbating disease progression. This work highlights that DMD hiPSC-skMCs demonstrate unique calcium signatures with increased intracellular calcium compared to healthy counterparts. These cells also exhibit both heightened calcium response when stimulated by electrical fields or acetylcholine and more pronounced constitutive calcium entries. While RNAseq data from these cells reaffirmed known dysregulation mechanisms seen in other dystrophin-deficient models, certain pathways like purinergic or store-operated calcium entries did not show disruption in this DMD model. This discrepancy suggests that not all mechanisms observed in animal models may be equally relevant in human cases, pointing towards specific molecular targets that could be more effective for DMD treatment strategies.

cell biology↗

bioRxiv2020

Polyunsaturated phospholipids increase cell resilience to mechanical constraints

Despite the fact that PolyUnsaturated Fatty Acids (PUFA) are generally accepted to be good for health, the mechanisms of their bona fide benefits still remain elusive. PUFA are particularly enriched in the membrane Phospholipids (PLs) of selective organs, among which skeletal muscles and the cardiovascular system are prime examples. The fatty acid composition of PLs is known to regulate crucial membrane properties, including rigidity, elasticity and plasticity. Since muscle cells undergo repeated cycles of elongation and relaxation and are constantly exposed to mechanical stress, we postulated in the present study that PUFA-containing PLs could be central players for muscle cell adaptation to mechanical constraints. By a combination of in cellulo and in silico approaches, we show that PUFA, and particularly the {omega}-3 DocoHexaenoic Acid (DHA), regulate important properties of the plasma membrane that improve muscle cell resilience to mechanical constraints. Thanks to their unique property to contortionate within the bilayer plane, they facilitate the formation of Vacuole-like dilation (VLD) which, in turn, reduce membrane stress and avoid cell breakage under mechanical constraints.

cell biology↗

bioRxiv2020

Fine tuning of calcium constitutive entry by optogenetically-controlled membrane polarization: impact on cell migration.

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as TRP, to be constitutively opened and strongly depend on membrane potential and calcium driving force. We developed an optogenetic approach based on expression of the halorhodopsin chloride pump to study CCE in non-excitable cells. Using C2C12 cells, we found that halorhodopsin can be used to achieve a finely-tuned control of membrane polarization. Escalating the membrane polarization by incremental changes in light led to a concomitant increase in CCE through TRPV2 channels. Moreover, light-induced calcium entry through TRPV2 channels promoted cell migration. Our study shows for the first time that by modulating CCE and related physiological responses such as cell motility, halorhodopsin serves as a potentially powerful tool that could open new avenues for the study of CCE and associated cellular behaviors.

cell biology↗

bioRxiv2019

A comprehensive study of Phospholipid fatty acid rearrangements in the early onset of the metabolic syndrome: correlations to organ dysfunction.

The balance within phospholipids (PL) between Saturated Fatty Acids (SFA) and mono- or poly-Unsaturated Fatty Acids (UFA), is known to regulate the biophysical properties of cellular membranes. As a consequence, perturbating this balance alters crucial cellular processes in many cell types, such as vesicular budding and the trafficking/function of membrane-anchored proteins. The worldwide spreading of the Western-diet, which is specifically enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome, known as the Metabolic Syndrome (MetS), which is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis. However, no clear correlations between diet-induced fatty acid redistribution within cellular PL, the severity/chronology of the symptoms associated to MetS and the function of the targeted organs, particularly in the early onset of the disease, have been established. In an attempt to fill this gap, we analyzed in the present study PL remodeling in rats exposed during 15 weeks to a High Fat/High Fructose diet (HFHF) in several organs, including known MetS targets. We show that fatty acids from the diet can distribute within PL in a very selective way, with PhosphatidylCholine being the preferred sink for this distribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the exception of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs.

biochemistry↗