A5040693338- Muscle Physiology and Disorders
- Virus-based gene therapy research
- RNA modifications and cancer
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- Muscle metabolism and nutrition
- Genetic Neurodegenerative Diseases
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Advanced Sensor and Energy Harvesting Materials
- Cardiovascular and exercise physiology
- Exercise and Physiological Responses
- Cellular Mechanics and Interactions
- Congenital heart defects research
Cincinnati Children's Hospital Medical Center
2017-2024
Abstract While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage multinucleation can be assignment distinct functions to different nuclei, but comprehensive interrogation transcriptional heterogeneity within multinucleated tissues has been challenging due presence shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) determine extent diversity myofibers. Nuclei...
Abstract Despite the importance of cell fusion for mammalian development and physiology, factors critical this process remain to be fully defined, which has severely limited our ability reconstitute fusion. Myomaker ( Tmem8c ) is a muscle-specific protein required myoblast Expression myomaker in fibroblasts drives their with myoblasts, but not other myomaker-expressing fibroblasts, highlighting requirement additional myoblast-derived Here we show that Gm7325 , name myomerger, induces...
Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control repair due severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that is required for growth using a supra-physiological model (Goh Millay, 2017), questions remained about need accrual adaptation in physiological setting. Here, developed an 8 week high-intensity interval training (HIIT) protocol assessed...
Muscle progenitor cell fusion is required for the formation and regeneration of multinucleated skeletal muscle fibers. Chronic in Duchenne muscular dystrophy (DMD) characterized by ongoing satellite (SC) progeny, but effects on disease mechanisms which accomplished this setting are not fully understood. Using mdx mouse model DMD, we deleted fusogenic protein Myomaker SCs or myofibers. Following deletion SCs, mice displayed a complete lack myocyte fusion, resulting severe loss, enhanced...
Multinucleated skeletal muscle cells have an obligatory need to acquire additional nuclei through fusion with activated stem when responding both developmental and adaptive growth stimuli. A fundamental question in biology has been the reason underlying this for new syncytial that already harbor hundreds of nuclei. To begin answer long-standing question, we utilized nuclear RNA-sequencing approaches developed a lineage tracing strategy capable defining transcriptional state recently fused...
Abstract While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage multinucleation can be assignment distinct functions to different nuclei, but comprehensive interrogation transcriptional heterogeneity within multinucleated tissues has been challenging due presence shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) determine extent diversity myofibers. Nuclei...
The development and maintenance of the neuromuscular junction (NMJ) requires reciprocal signals between nerve terminals multinucleated skeletal muscle fiber (myofiber). This interaction leads to highly specialized transcription in sub-synaptic or NMJ myonuclei within mature myofibers leading clustering acetylcholine receptors (AChRs). Here, we utilized single-nucleus RNA sequencing (snRNA-seq) delineate transcriptional response denervation. Through snRNA-seq on from two independent mouse...
Abstract Despite the importance of cell fusion for mammalian development and physiology, factors critical this process remain to be fully defined 1 . This lack knowledge has severely limited our ability reconstitute fusion, which is necessary decipher biochemical mechanisms driving plasma membrane merger. Myomaker ( Tmem8c ) a muscle-specific protein required myoblast 2,3 Expression myomaker in fibroblasts drives their with myoblasts, but not other myomaker-fibroblasts, highlighting...
Entry of enveloped viruses into cells is mediated by fusogenic proteins that form a complex between membranes to drive rearrangements needed for fusion. Skeletal muscle development also requires membrane fusion events progenitor multinucleated myofibers. Myomaker and Myomerger are muscle-specific cell fusogens, but do not structurally or functionally resemble classical viral fusogens. We asked if the fusogens could substitute despite their structural distinctiveness, fuse cells. report...