Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stagespecific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair.

SUMMARY Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and aggressive type of soft tissue sarcoma, can develop in this context, but the impact of DMD severity on RMS development and its cell of origin are poorly understood. Here, we show that RMS latency is affected by DMD severity and that muscle stem cells (MuSCs) can give rise to RMS in dystrophic mice. We report that even before tumor formation, MuSCs exhibit increased self-renewal and an expression signature associated with RMSs. These cells can form tumorspheres in vitro and give rise to RMSs in vivo. Finally, we show that the inflammatory genes Ccl11 and Rgs5 are involved in RMS growth. Together, our results show that DMD severity drives MuSC-mediated RMS development.

Phenolic compounds in fruit provide human health benefits, and they contribute to color, taste, and the preservation of post-harvest fruit quality. Phenolic compounds also serve as modifiers of enzymatic activity, whether inhibition or stimulation. Polyphenol oxidases (PPO) and peroxidases (POD) use phenolic compounds as substrates in oxidative browning. Apple browning leads to flesh color, taste, texture, and flavor degradation, representing a drawback for the variety and its’ market appraisal. This study was conducted to investigate the process of browning in 14 apple cultivars throughout post-harvest at three-time points: immediately (T0), one hour (T1), and 24 h (T2) after apples were cut in half. Color parameters L* (lightness), a* (red/green), b* (yellow/blue) were measured, and chroma (ΔC*) and color (ΔE) were calculated to quantify differences between T0₋T1 and T1₋T2 on the fruit surface. Enzymatic activity (PPO, POD) and phenolic composition were also quantified for each cultivar. ‘Granny Smith’ and ‘Cripps Pink’ browned minimally. In contrast, ‘Fiesta’ and ‘Mondial Gala’ browned severely, reporting high enzymatic activity and quantified phenolic concentration (QPC). Phenolic compound polymerization appears to play a significant role in enzymatic inhibition. ‘Topaz’ does not fit the high QPC, PPO, and browning formula, suggesting alternative pathways that contribute to apple browning.