Biology subjects

Bourlier, V.

Publications and source records attributed to Bourlier, V..

3 recordsLinked to original sources

bioRxiv2025

Mobilizable adipose stromal cells fuel regenerative adipogenesis in injured muscle

Skeletal muscle regeneration is a highly orchestrated process involving the dynamic interplay of multiple cell types. Among these, fibro-adipogenic progenitors (FAPs), a population of resident mesenchymal stromal cells (MSCs), are essential for creating a supportive microenvironment that promotes satellite cell differentiation and modulates immune responses. Our recent work revealed that adipose stromal cells (ASCs) from subcutaneous adipose tissue (ScAT) infiltrate the injured muscle within the first 24h post-injury, contributing significantly to the regenerative process. Consequently, the FAP population in the regenerating muscle comprises both resident FAPs and infiltrated ASCs. In the present study, using single cell RNA-seq in a mouse model with trackable KikGR+ ASCs and bioinformatics analyses, we identify Limch1+/Prg4+ ASCs as the primary Mobilizable ASCs (Mob-ASCs) that migrate to and infiltrate the injury site. Notably, this migration is detectable as early as 14 hours post-injury. We demonstrate that these cells are pre-activated within the ScAT, primed to initiate both migratory and regenerative programs. Intriguingly, bioinformatic inference of key activated transcription factors suggested that adipogenesis is also activated in these cells. Leveraging supervised machine learning, we tracked the fate of Mob-ASCs within the regenerating muscle post-injury, where they continue to execute these programs. Importantly, these cells lineage is cued towards a fate of adipogenesis. In vivo, we observed transient generation of adipocytes with a peak at 7-9 days post-injury to which infiltrated ASCs contributed. In vitro, conditioned media assays further revealed that adipocytes derived from ASCs--but not those from FAPs--enhance myoblasts fusion. Collectively, our findings establish Limch1+/Prg4+ ASCs as the Mobilizable ASC population and suggest that their transient adipogenic differentiation is beneficial for muscle regeneration.

physiology↗

bioRxiv2020

GREM1 is epigenetically reprogrammed in muscle cells after exercise training and controls myogenesis and metabolism

Exercise training improves skeletal muscle function, notably through tissue regeneration by muscle stem cells. Here, we hypothesized that exercise training reprograms the epigenome of muscle cell, which could account for better muscle function. Genome-wide DNA methylation of myotube cultures established from middle-aged obese men before and after endurance exercise training identified a differentially methylated region (DMR) located downstream of Gremlin 1 (GREM1), which was associated with increased GREM1 expression. GREM1 expression was lower in muscle satellite cells from obese, compared to lean mice, and exercise training restored GREM1 levels to those of control animals. We show that GREM1 regulates muscle differentiation through the negative control of satellite cell self-renewal, and that GREM1 controls muscle lineage commitment and lipid oxidation through the AMPK pathway. Our study identifies novel functions of GREM1 and reveals an epigenetic mechanism by which exercise training reprograms muscle stem cells to improve skeletal muscle function.

cell biology↗

bioRxiv2019

Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non shivering thermogenesis

Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and arterial pressure in mammals. It is unclear whether and how ANP controls cold-induced thermogenesis in vivo. Here we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses about half of cold-induced brown adipose tissue (BAT) activation in mice. While white adipocytes are resistant to ANP-mediated lipolysis at thermoneutral temperature in mice, cold exposure renders white adipocytes fully responsive to ANP to activate lipolysis and a thermogenic program, a physiological response which is dramatically suppressed in ANP null mice. ANP deficiency also blunts liver triglycerides and glycogen metabolism thus impairing fuel availability for BAT thermogenesis. ANP directly increases mitochondrial uncoupling and thermogenic genes expression in human white and brown adipocytes. Together, these results indicate that ANP is a major physiological trigger of BAT thermogenesis upon cold exposure in mammals.

physiology↗