Biology subjects

Kong, Y.-Y.

Publications and source records attributed to Kong, Y.-Y..

4 recordsLinked to original sources

bioRxiv2026

Terminal Schwann Cells Regulate Presynaptic Vesicle Homeostasis but Not Neuromuscular Junction Integrity in Mice

Terminal Schwann cells (tSCs) are specialized glial cells persistently residing at the neuromuscular junction (NMJ), where they are widely postulated to participate in synaptic transmission and maintenance. However, elucidating their precise in vivo roles has been hindered by a lack of tSC-specific genetic models, as conventional tools simultaneously targeted axonal Schwann cells. Here, we identify Col20a1 as a highly specific marker for tSCs through single-cell transcriptomic analysis and establish a novel Col20a1-CreERT2 knock-in mouse model. Utilizing this model, we achieved highly specific systemic labeling and ablation of tSCs during the postnatal maturation window. Surprisingly, systemic tSC loss disrupted neither gross NMJ architecture nor overall motor behavior. Instead, electrophysiological and ultrastructural analyses revealed profound pre-synaptic defects, characterized by increased spontaneous miniature endplate potentials (mEPPs), accelerated synaptic depression during high-frequency stimulation, and significant physical depletion of pre-synaptic vesicles. Furthermore, long-term analysis revealed a robust glial repopulation that sustained prolonged neuromuscular integrity. Together, our findings establish Col20a1 as a definitive genetic handle for tSC research, delineating that while tSCs are dispensable for macroscopic synaptic structure, they serve a precise and critical role in regulating pre-synaptic vesicle homeostasis.

neuroscience↗

bioRxiv2025

Rejuvenation-Responsive and Senolytic-Sensitive Muscle Stem Cells Unveiled by CD200 and CD63 in Geriatric Muscle

Muscle stem cells (MuSCs) are parenchymal cells in skeletal muscle regeneration and maintenance. With aging, MuSCs experience a decline in their regenerative function and reduction in their number. However, recent evidence points to substantial heterogeneity within the aged MuSC population, raising questions about the underlying mechanisms of age-associated dysfunction. Here, we used Pax7CreERT2;RosaYFP mice (MuSCYFP) to label Pax7-expressing MuSCs and chronologically traced MuSCs until geriatric age. Genetic labeling and chronological tracing revealed that the number of YFP+ MuSC remained comparable between young, middle and geriatric ages. At geriatric age, YFP+ MuSCs exhibited reduced expression of traditional MuSC markers such as VCAM1 and PAX7. A previously unrecognized subpopulation emerged, characterized by loss of VCAM1 and low or absent PAX7. Despite their altered marker profile, these cells retained transcriptional signatures of quiescence and myogenic potential, but displayed significantly reduced proliferative and regenerative capacities. They displayed gene expression patterns indicative of senescence-like state and were selectively ablated by senolytic treatment. DHT restored regenerative function in aged mice and re-induced VCAM1 expression in YFP+/Pax7-/low/VCAM1- cells, indicating responsiveness to rejuvenation. Based on their emergence with aging, functional impairment and responsiveness to rejuvenation, we termed this population GERI-MuSCs (Geriatric Emerging Rejuvenation-responsive and Impaired MuSCs). CD63 and CD200 were identified as novel surface markers that together with VCAM1, reliably detect GERI-MuSCs as well as classical Pax7+/VCAM1High MuSCs, providing a tool for comprehensive isolation of MuSCs from aged wild-type mice. Together, our findings provide a refined framework for studying MuSC aging and offer new tools for isolating functionally distinct MuSC subsets from aged skeletal muscle.

developmental biology↗

bioRxiv2024

Muscle-resident mesenchymal progenitors sense and repair peripheral nerve injury via the GDNF-BDNF axis

Fibro-adipogenic progenitors (FAPs) are muscle-resident mesenchymal progenitors that can contribute to muscle tissue homeostasis and regeneration, as well as postnatal maturation and lifelong maintenance of the neuromuscular system. Recently, traumatic injury to the peripheral nerve was shown to activate FAPs, suggesting that FAPs can respond to nerve injury. However, questions of how FAPs can sense the anatomically distant peripheral nerve injury and whether FAPs can directly contribute to nerve regeneration remained unanswered. Here, utilizing single-cell transcriptomics and mouse models, we discovered that a subset of FAPs expressing GDNF receptors Ret and Gfra1 can respond to peripheral nerve injury by sensing GDNF secreted by Schwann cells. Upon GDNF sensing, this subset becomes activated and expresses Bdnf. FAP-specific inactivation of Bdnf (Prrx1Cre; Bdnffl/fl) resulted in delayed nerve regeneration owing to defective remyelination, indicating that GDNF-sensing FAPs play an important role in the remyelination process during peripheral nerve regeneration. In aged mice, significantly reduced Bdnf expression in FAPs was observed upon nerve injury, suggesting the clinical relevance of FAP-derived BDNF in the age-related delays in nerve regeneration. Collectively, our study revealed the previously unidentified role of FAPs in peripheral nerve regeneration, and the molecular mechanism behind FAPs response to peripheral nerve injury.

neuroscience↗

bioRxiv2023

Depletion of SMN Protein in Mesenchymal Progenitors Impairs the Development of Bone and Neuromuscular Junction in Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cells (MPCs)-specific SMN-depleted mouse models, we reveal that SMN reduction in chondrocytes and fibro-adipogenic progenitors (FAPs) derived from limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ), respectively. We showed that impaired growth plate homeostasis, which causes skeletal growth defects in SMA, is due to reduced IGF signaling from chondrocytes rather than the liver. Furthermore, the reduction of SMN in FAPs resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis in SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.

neuroscience↗