Biology subjects

Evano, B.

Publications and source records attributed to Evano, B..

5 recordsLinked to original sources

bioRxiv2025

Impaired stem cell migration and divisions in Duchenne Muscular Dystrophy revealed by live imaging

Dysregulation of stem cell properties is a hallmark of many pathologies, but the dynamic behaviour of stem cells in their microenvironment during disease progression remains poorly understood. Using the mdx mouse model of Duchenne Muscular Dystrophy, we developed innovative live-imaging of muscle stem cells (MuSCs) in vivo, and ex vivo on isolated myofibres. We show that mdx MuSCs have impaired migration and precocious differentiation through unbalanced symmetric divisions, driven by p38 and PI3K signalling pathways, in contrast to the p38-only dependence of healthy MuSCs. Cross-grafting shows that MuSC fate decisions are governed by intrinsic cues, whereas their migration behaviour is determined by the extracellular niche. This study provides the first dynamic analysis of dystrophic MuSC properties in vivo, reconciling conflicting reports on their function. Our findings establish DMD as a MuSC disease with intrinsic defects and niche dysfunction, offering strategies to restore stem cell functions for improved muscle regeneration.

cell biology↗

bioRxiv2023

Extraocular muscle stem cells exhibit distinct cellular properties associated with non-muscle molecular signatures

The muscle stem cell (MuSC) population is recognized as functionally heterogeneous. Cranial muscle stem cells, which originate from head mesoderm, can have greater proliferative capacity in culture and higher regenerative potential in transplantation assays when compared to those in the limb. The existence of such functional differences in phenotypic outputs remain unresolved as a comprehensive understanding of the underlying mechanisms is lacking. We addressed this issue using a combination of clonal analysis, live imaging, and scRNA-seq, identifying critical biological features that distinguish extraocular (EOM) and limb (Tibialis anterior, TA) MuSC populations. Time-lapse studies using a MyogenintdTomatoreporter showed that the increased proliferation capacity of EOM MuSCs is accompanied by a differentiation delay in vitro. Unexpectedly, in vitro activated EOM MuSCs expressed a large array of distinct extracellular matrix (ECM) components, growth factors, and signaling molecules that are typically associated with mesenchymal non-muscle cells. These unique features are regulated by a specific set of transcription factors that constitute a coregulating module. This transcription factor network, which includes Foxc1 as one of the major players, appears to be hardwired to EOM identity as it is present in quiescent adult MuSCs, in the activated counterparts during growth and retained upon passages in vitro. These findings provide insights into how high-performing MuSCs regulate myogenic commitment by active remodeling of their local environment.

developmental biology↗

bioRxiv2020

Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation

Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.

molecular biology↗

bioRxiv2018

Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in muscle stem cells

Age-related tissue alterations have been associated with a decline in stem cell number and function1. Although increased cell-to-cell variability in transcription or epigenetic marks has been proposed to be a major hallmark of ageing2-5, little is known about the molecular diversity of stem cells during ageing. Here, by combined single-cell transcriptome and DNA methylome profiling in mouse muscle stem cells, we show a striking global increase of uncoordinated transcriptional heterogeneity together with context-dependent alterations of DNA methylation with age. Importantly, promoters with increased methylation heterogeneity are associated with increased transcriptional heterogeneity of the genes they drive. Notably, old cells that change the most with age reveal alterations in the transcription of genes regulating cell-niche interactions. These results indicate that epigenetic drift, by accumulation of stochastic DNA methylation changes in promoters, is a substantial driver of the degradation of coherent transcriptional networks with consequent stem cell functional decline during ageing.

genomics↗

bioRxiv2018

Differential cell fates of muscle stem cells are accompanied by symmetric segregation of canonical H3 histones in vivo

Stem cells are maintained through symmetric or asymmetric cell divisions. While various mechanisms initiate asymmetric cell fates during mitosis, possible epigenetic control of this process has emerged recently. The asymmetrical distribution of a canonical histone H3 variant during mitosis in fly germline has suggested a role for partitioning old and new nucleosomes in asymmetric cell fates. Here, we provide resources for single cell assays and show the asymmetric segregation of transcription factors along with old and new DNA in mouse muscle stem cells ex vivo and in vivo. However, these differential fate outcomes contrast with a symmetric distribution of the canonical H3.1 vertebrate variant. These findings point to different evolutionary mechanisms operating in fly germline stem cells and vertebrate somatic stem cells to mitigate epigenetic regulation of asymmetric cell fates.

cell biology↗