The Mediator Med23 controls a transcriptional switch for muscle stem cell proliferation and differentiation in muscle regeneration.

Muscle stem cells (MuSCs) contribute to a robust muscle regeneration process after injury, which is highly orchestrated by the sequential expression of multiple key transcription factors. However, it remains unclear how key transcription factors and cofactors such as the Mediator complex cooperate to regulate myogenesis. Here, we show that the Mediator Med23 is critically important for MuSC-mediated muscle regeneration. Med23 is increasingly expressed in activated/proliferating MuSCs on isolated myofibers or in response to muscle injury. Med23 deficiency reduced MuSC proliferation and enhanced its precocious differentiation, ultimately compromising muscle regeneration. Integrative analysis revealed that Med23 oppositely impacts Ternary complex factor (TCF)-targeted MuSC proliferation genes and myocardin-related transcription factor (MRTF)-targeted myogenic differentiation genes. Consistently, Med23 deficiency decreases the ETS-like transcription factor 1 (Elk1)/serum response factor (SRF) binding at proliferation gene promoters but promotes MRTF-A/SRF binding at myogenic gene promoters. Overall, our study reveals the important transcriptional control mechanism of Med23 in balancing MuSC proliferation and differentiation in muscle regeneration.

Multifunctional Ternary Hybrid Hydrogel Sensor Prepared via the Synergistic Stabilization Effect.

Since highly stretchable hydrogels have demonstrated their promising applications in flexible tactile sensors and wearable devices, the current challenge has been imposed on stretchable and multifunctional electronics. Here, we report a multifunctional sensor composed of a liquid metal (LM) nanodroplet-adhered self-assembled polymeric network, anionic carboxymethylcellulose (CMC), and cationic polyacrylamide (PAAm). The synergistic effect, zeta potential reduction, by CMC and macromolecules enveloped by LM contributes to the stabilization of the ternary system during preparation and, thus, the homogenization of the products. By engineering and optimizing the ternary hybrid hydrogels, excellent extensibility (tensile strain near 300%), readily reversible hysteresis loops, and accessible deformability (low modulus of 104 Pa) are afforded. The fabricated sensor exhibits a high tensile strain gauge factor of around 0.7 and a high compressive stress sensitivity of up to 0.12 kPa-1, a fast response time below 125 ms, and a high stability and precision in usage. In a series of practical scenarios, the assembled sensor displays distinguished abilities to monitor bodily motions, record electrocardiograms, authenticate handwriting, discern temperature, and infer materials, making them highly promising for multifunctional intelligent soft sensing.