Single‐Nucleus Atlas of Spinal Sarcopenia Patients Reveals Disruption of Quiescent and Regenerative Satellite Cell Niches in Fatty‐Infiltrated Muscle

ABSTRACT Severe muscle fat infiltration is a contributing factor to muscle loss, particularly in the spinal sarcopenia population. However, the underlying mechanism largely remains elusive. Here, we identified the intramuscular fat fraction (IMFF), rather than perimuscular fat fraction, as an independent determinant of trunk muscle strength. Individuals with higher IMFF (10‐15% and >15%) exhibited significantly lower paraspinal muscle mass and strength compared to those with lower IMFF (+ fibro/adipogenic progenitor (FAP) subpopulation with enhanced lipogenic potential, characterized by high expression of GPC3, PPARG, ADIPOQ, and FABP4, representing a transition from MME high GPC3 low FAPs into MME low GPC3 high adipogenic FAPs. Collectively, our findings delineate the cellular landscape and signaling interactions that underlie pathological fat infiltration in spinal muscles, providing mechanistic insight and potential therapeutic targets for spinal sarcopenia.