Biology subjects

Song, I.-W.

Publications and source records attributed to Song, I.-W..

3 recordsLinked to original sources

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↗

bioRxiv2020

COPB2 haploinsufficiency causes a coatopathy with osteoporosis and developmental delay

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures and developmental delay of variable severity. Because the role of COPB2 in bone has not been characterized, we studied the effect of COPB2 deficiency on skeletal development in mice and zebrafish. Copb2+/- mice showed low bone mass and decreased bone strength. In zebrafish, larvae carrying a copb2 heterozygous frameshift variant showed delayed mineralization. copb2-null embryos showed endoplasmic reticulum (ER) and Golgi disorganization, and embryonic lethality. COPB2 siRNA-treated fibroblasts showed delayed collagen trafficking with retention of type I collagen in the ER and Golgi, and altered distribution of Golgi markers. Our data suggest that COPB2 haploinsufficiency leads to disruption of intracellular collagen trafficking and osteoporosis, which may improve with ascorbic acid supplementation. This work highlights the role of COPI complex as a critical regulator of bone mass and identifies a new form of coatopathy due to COPB2 deficiency.

genetics↗