Biology subjects

Sage, F.

Publications and source records attributed to Sage, F..

3 recordsLinked to original sources

bioRxiv2026

Sex-specific DNA methylation in adult skeletal muscle

DNA methylation is a key epigenetic mechanism influencing gene regulation and cellular identity. In skeletal muscle, methylation contributes to fiber-type specification, metabolic programming, and satellite cell function, with evidence of sex-specific differences. Here, we investigated whether spatial regionalization of gene expression along the proximal-distal axis of the tibialis anterior (TA) is mirrored by corresponding patterns of DNA methylation. Using MeDseq on TA sections from muscles previously analyzed by spatial transcriptomics, we profiled methylation across transcriptional start sites (TSS), gene bodies, and regulatory elements. Despite robust spatial differences in transcriptomes, methylation patterns were largely uniform along the proximal-distal axis, indicating that DNA methylation does not underlie regional gene expression in adult TA muscle. In contrast, sex emerged as the primary determinant of methylation variation. Male muscles exhibited widespread hypermethylation at TSS, gene-bodies and regulatory regions, corresponding with sex-specific transcriptional programs, including glycolytic fiber enrichment in males and oxidative fiber markers in females. Notably, chromatin- and methylation-associated regulators such as Setd7, Gsk3a, and Bmyc were upregulated in males, suggesting mechanisms linking transcriptional control to epigenetic state. These findings highlight that while spatial gene expression is transcriptionally driven, sex-specific epigenetic programs dominate adult skeletal muscle, underscoring the need to consider sex in multi-omic studies of muscle biology.

molecular biology↗

bioRxiv2023

3D printed magneto-active microfiber scaffolds for remote stimulation of 3D in vitro skeletal muscle models

Tunable culture platforms that guide cellular organization and mechanically stimulate skeletal muscle development are still unavailable due to limitations in biocompatibility and actuation triggered without contact. This study reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a thermoplastic/graphene/iron oxide composite. In situ deposition of iron oxide nanoparticles on oxidized graphene yielded homogeneously dispersed magnetic particles with sizes above 0.5 m and low aspect ratio, preventing cellular internalization and toxicity. With these fillers, homogeneous magnetic composites with very high magnetic filler content (up to 10 wt.%) were obtained and successfully processed in a solvent-free manner for the first time. MEW of magnetic composites enabled the skeletal muscle-inspired design of hexagonal scaffolds with tunable fiber diameter, reconfigurable modularity, and zonal distribution of magneto-active and nonactive material. Importantly, the hexagonal microstructures displayed elastic deformability under tension, mitigating the mechanical limitations due to high filler content. External magnetic fields below 300 mT were sufficient to trigger out-of-plane reversible deformation leading to effective end-to-end length decrease up to 17%. Moreover, C2C12 myoblast culture on 3D Matrigel/collagen/MEW scaffolds showed that the presence of magnetic particles in the scaffolds did not significantly affect viability after 8 days with respect to scaffolds without magnetic filler. Importantly, in vitro culture demonstrated that myoblasts underwent differentiation at similar rates regardless of the presence of magnetic filler. Overall, these innovative microfiber scaffolds were proven as a magnetically deformable platform suitable for dynamic culture of skeletal muscle with potential for in vitro disease modeling.

bioengineering↗

bioRxiv2021

DUX4 induces a homogeneous sequence of molecular changes, culminating in the activation of a stem-cell-like transcriptional network and induction of apoptosis in somatic cells

Facioscapulohumeral muscular dystrophy (FSHD) is a muscle degenerative disease that disproportionally affects the muscles of the face, shoulder girdle and upper arms. FSHD is caused by the misexpression of Double Homeobox 4 (DUX4), a transcription factor that is normally expressed during early embryonic development. Ectopic expression of DUX4 in somatic cells is cytotoxic and leads to rapid apoptosis. To elucidate the mechanism by which DUX4 induces apoptosis, we determined the temporal transcriptional changes induced by Dux4 at the single-cell level. We observed that induction of DUX4 expression induces a non-random, consecutive sequence of transcriptional changes. DUX4 homogenously induces the activation of a stem cell signature and activates a network of transcription factors that is typically expressed during early embryogenesis and in pluripotent stem cells. Ultimately, these transcriptional changes trigger the induction of apoptosis, suggesting that the induction of this early stemness program is incompatible with a somatic cell program. Our findings shed new light on the timing and dynamic of DUX4-mediated transcriptional reprogramming and may help elucidate why the DUX4 stemness program is required during early embryogenesis, but incompatible with somatic cell viability.

molecular biology↗