A5059197674- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- RNA Research and Splicing
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Extracellular vesicles in disease
- Mesenchymal stem cell research
- GDF15 and Related Biomarkers
- Single-cell and spatial transcriptomics
- Cerebral Palsy and Movement Disorders
- Down syndrome and intellectual disability research
- Cancer-related molecular mechanisms research
- Telomeres, Telomerase, and Senescence
- Neurogenetic and Muscular Disorders Research
- Adipose Tissue and Metabolism
- Amyotrophic Lateral Sclerosis Research
University of Colorado Boulder
2012-2023
Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident cells or satellite are required for growth repair, in uninjured muscle, these appear quiescent metabolically inactive. To investigate the cell contribution myofibers adult we labeled by inducing a recombination LSL-tdTomato Pax7CreER mice scoring tdTomato+ as an indicator fusion. Satellite fusion into plateaus postnatally between 8 12 weeks age, reaching steady...
Skeletal muscle stem cells, or satellite cells (SCs), are essential to regenerate and maintain muscle. Quiescent SCs reside in an asymmetric niche between the basal lamina myofiber membrane. To repair muscle, activate, proliferate, differentiate, fusing myofibers reacquiring quiescence replenish SC niche. Little is known about when reacquire during regeneration cellular processes that direct fate decisions. We find most 5-10 days after injury, following differentiation fusion of myofibers....
Satellite cells are resident skeletal muscle stem responsible for maintenance and repair. In resting muscle, satellite maintained in a quiescent state. cell activation induces the myogenic commitment factor, MyoD, cycle entry to facilitate transition population of proliferating myoblasts that eventually exit regenerate tissue. The molecular mechanism involved transit-amplifying myoblast is poorly understood.Satellite isolated by FACS from uninjured 12 h post-muscle injury wild type...
The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in supports communication with the niche, providing interactions signals to maintain cells. Syndecan-3 ablation unexpectedly improves regeneration repeatedly injured dystrophic mice, accompanied by persistence of sublaminar interstitial, proliferating myoblasts. Additionally, aging is improved...
RNA-binding proteins (RBPs), essential for skeletal muscle regeneration, cause degeneration and neuromuscular disease when mutated. Why mutations in these ubiquitously expressed RBPs orchestrate complex tissue regeneration direct cell fate decisions remains poorly understood. Single-cell RNA-sequencing of regenerating Mus musculus reveals that RBP expression, including the expression many disease-associated RBPs, is temporally regulated stem cells correlates with specific stages myogenic...
Skeletal muscle function and regenerative capacity decline during aging, yet factors driving these changes are incompletely understood. Muscle regeneration requires temporally coordinated transcriptional programs to drive myogenic stem cells activate, proliferate, fuse form myofibers, mature as myonuclei, restoring after injury. We assessed global in transcription distinguishing aged mice from young by comparing pseudotime trajectories single-nucleus RNA sequencing of nuclei. Aging-specific...
Summary Skeletal muscle stem cells (MuSCs) are essential for regeneration and maintenance. While MuSCs typically quiescent reside in an asymmetric niche between the basal lamina myofiber membrane: to repair or maintain muscle, activate, proliferate differentiate injured tissue, self-renew replenish MuSCs. Little is known about timing of MuSC self-renewal during cellular processes that direct fate decisions. Using DNA-based lineage tracing, we find most from 5-7 days post-injury, following...
Down syndrome, caused by trisomy 21, is characterized a variety of medical conditions including intellectual impairments, cardiovascular defects, blood cell disorders and pre-mature aging phenotypes. Several somatic stem populations are dysfunctional in syndrome their deficiencies may contribute to multiple associated with muscle weakness but skeletal cells or satellite have not been investigated. We find that failure expansion impairs regeneration the Ts65Dn mouse model syndrome. accumulate...
Summary Skeletal muscle maintenance and repair is dependent on the resident adult stem cell (MuSC). During injury, in diseased muscle, cells are engaged to replace or damaged which requires exit quiescence expand, followed by differentiation regenerate myofibers self-renewal replenish population. Following an little known regarding timing of MuSC (skeletal cell) self-renewal, myoblast expansion differentiation. To determine kinetics these fate decisions, we employed DNA-based lineage tracing...
ABSTRACT RNA-binding proteins (RBPs) are essential for skeletal muscle regeneration and RBP dysfunction causes degeneration neuromuscular disease. How ubiquitously expressed RBPs orchestrate complex tissue direct cell fate decisions in remains poorly understood. Single RNA-sequencing of regenerating reveals that expression, including numerous disease-associated RBPs, is temporally regulated stem cells correlates to stages myogenic differentiation. By combining machine learning with...
Abstract Skeletal muscle cells are multinucleated syncytial arising from cell fusion, yet despite sharing a common cytoplasm individual myonuclei express distinct transcriptional programs. Whether acquire heterogenous states via differences in their progenitors, during differentiation, or once anatomical position is acquired, not known. We performed transcriptome and pseudotime analysis of single myogenic nuclei uninjured post-injury murine skeletal to assess when myonuclear heterogeneity...