A5063871472- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Developmental Biology and Gene Regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Congenital heart defects research
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Mesenchymal stem cell research
- RNA Research and Splicing
- Diet and metabolism studies
- Sirtuins and Resveratrol in Medicine
- Nuclear Receptors and Signaling
- Genomics, phytochemicals, and oxidative stress
- PI3K/AKT/mTOR signaling in cancer
- Neurogenetic and Muscular Disorders Research
- Marine Biology and Environmental Chemistry
- RNA Interference and Gene Delivery
- Animal Genetics and Reproduction
- Cardiovascular Disease and Adiposity
- Microtubule and mitosis dynamics
University of Georgia
2019-2024
The University of Texas Southwestern Medical Center
2017-2018
Purdue University West Lafayette
2011-2017
State Street (United States)
2017
University of Minnesota Medical Center
2012
Stem Cell Institute
2012
Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required myoblast and myogenesis, we discovered an 84-amino acid muscle-specific peptide that call Myomixer. Myomixer expression coincides with differentiation is essential skeletal during embryogenesis. localizes the plasma membrane, where it promotes associates Myomaker,...
Myostatin (Mstn) is predominantly expressed in skeletal muscles and plays important roles regulating muscle growth development, as well fat deposition. Mstn-knockout (Mstn(-/-)) mice exhibit increased mass due to both hypertrophy hyperplasia, leaner body composition reduced mass. Here, we show that white adipose tissue (WAT) of Mstn(-/-) develops characteristics brown (BAT) with dramatically expression BAT signature genes, including Ucp1 Pgc1α, beige adipocyte markers Tmem26 CD137....
d Notch signaling is a conserved cell fate regulator during development and postnatal tissue regeneration.Using skeletal muscle satellite cells as model through myogenic lineage-specific NICD OE (overexpression of constitutively activated 1 intracellular domain), here we investigate how regulates the choice stem cells.We show that in addition to inhibiting MyoD differentiation, upregulates Pax7 promotes self-renewal cell-derived primary myoblasts culture.Using ؊/؊ myoblasts, further...
Microenvironmental oxygen (O2) regulates stem cell activity, and a hypoxic niche with low levels has been reported in multiple types. Satellite cells are muscle-resident that maintain the homeostasis mediate regeneration of skeletal muscles. We demonstrate here culture conditions favor quiescence satellite cell-derived primary myoblasts by upregulating Pax7, key regulator self-renewal, downregulating MyoD myogenin. During myoblast division, hypoxia promotes asymmetric self-renewal divisions...
Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose tissue (BAT) and regulates thermogenic gene program subcutaneous white (SAT) in mice. Here we show that miR-133a, a microRNA is expressed both BAT SATs, directly targets 3′ UTR Prdm16. The expression miR-133a dramatically decreases along commitment differentiation brown preadipocytes, accompanied by upregulation Overexpression SAT cells significantly inhibits, conversely inhibition upregulates, adipogenesis....
Abstract Satellite cells (SCs) are myogenic stem required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential long-term maintenance SCs their regenerative function. Here we show a function Pten (phosphatase tensin homologue) in quiescent SCs. Deletion leads to spontaneous premature without proliferation, resulting depletion SC pool failure. However, prior depletion, -null activated can transiently proliferate upon injury...
Skeletal myogenesis involves sequential activation, proliferation, self-renewal/differentiation and fusion of myogenic stem cells (satellite cells). Notch signaling is known to be essential for the maintenance satellite cells, but its function in late-stage myogenesis, i.e. post-differentiation myocytes post-fusion myotubes, unknown. Using stage-specific Cre alleles, we uncovered distinct roles Notch1 mononucleated multinucleated myotubes. Specifically, constitutive activation...
Brown adipose tissue (BAT) dissipates energy through Ucp1-mediated uncoupled respiration and its activation may represent a therapeutic strategy to combat obesity. Here we show that Lkb1 controls BAT expansion UCP1 expression in mice. We generate adipocyte-specific knockout mice that, compared with wild-type littermates, these exhibit elevated subcutaneous white tissue, have increased mass higher expenditure. Consequently, KO improved glucose tolerance insulin sensitivity, are more resistant...
Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of lack animal models, cellular origin and molecular regulation LPS remain unclear. Here, we report that mice with adipocyte-specific activation Notch signaling (Ad/N1ICD) develop complete penetrance. Lineage tracing confirms adipocyte Ad/N1ICD LPS. The resembles human dedifferentiated in histological appearance, anatomical localization, gene expression signature. Before transformation, adipocytes undergo dedifferentiation...
Significance Skeletal muscle damaged by injury or disease can regenerate new fibers. The regenerative properties of skeletal involve fusion activated stem cells (satellite cells). We recently discovered Myomixer, a conserved micropeptide that is specifically expressed during formation. together with its partner Myomaker, another muscle-specific membrane protein, necessary for formation embryogenesis. Here, we show the absolute requirement Myomixer satellite and regeneration adult in response...
MyoD–Myomixer/Myomaker axis controls human myoblast fusion.
Brown adipose tissues (BAT) are derived from a myogenic factor 5 (Myf5)-expressing cell lineage and white (WAT) predominantly arise non-Myf5 lineages, although subpopulation of adipocytes in some WAT depots can be the Myf5 lineage. However, functional implication Myf5- non-Myf5-lineage cells is unclear. We found that Myf5-lineage constitution subcutaneous negatively correlated to expression classical BAT newly defined beige/brite adipocyte-specific genes. Consistently, fluorescent-activated...
One outcome of activation the phosphatidylinositol 3-kinase (PI3K) pathway is increased aerobic glycolysis, but upstream signaling events that regulate PI3K pathway, and thus Warburg effect, are elusive. Increasing evidence suggests Plk1, a cell cycle regulator, also involved in cellular addition to mitosis. To test whether Plk1 contributes we examined potential targets identified PTEN as substrate. We hypothesize phosphorylation leads its inactivation, effect. Our data show overexpression...
Skeletal muscle stem cells (satellite [SCs]) are normally maintained in a quiescent (G0) state. Muscle injury not only activates SCs locally, but also alerts distant uninjured muscles via circulating factors. The resulting GAlert adapted to regenerative cues and regenerate injured more efficiently, whether they provide any long-term benefits is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase tensin homolog (Pten) exhibit enhanced proliferation...
Serine/threonine kinase 11, commonly known as liver b1 (Lkb1), is a tumor suppressor that regulates cellular energy metabolism and stem cell function. Satellite cells are skeletal muscle resident maintain postnatal growth repair. Here, we used MyoD(Cre)/Lkb1(flox/flox) mice (called MyoD-Lkb1) to delete Lkb1 in embryonic myogenic progenitors their descendant satellite myofibers. The MyoD-Lkb1 exhibit severe myopathy characterized by central nucleated myofibers, reduced mobility, retardation,...
Significance The formation of skeletal muscle fibers during embryogenesis and adult injury-induced repair occurs through the fusion myoblasts. We recently discovered myomixer, a muscle-specific micropeptide required for myoblast in mice. Myomixer myomaker, another membrane protein, are sufficient to induce nonmuscle cells. Here, we extend these findings demonstrate requirement myomixer zebrafish fusion. also striking functional conservation zebrafish, elephant shark, turtle among other...
Excessive intramyocellular triglycerides (muscle lipids) are associated with reduced contractile function, insulin resistance, and Type 2 diabetes, but what governs lipid accumulation in muscle is unclear. Here we report a role of Lkb1 regulating metabolism stem cells their descendent mature muscles. We used Myod(Cre) Lkb1(flox/flox) mice to specifically delete myogenic including differentiated cells, examined the gene expression myoblasts cultured from (satellite cells). Genetic deletion...
Vertebrate myoblast fusion allows for multinucleated muscle fibers to compound the size and strength of mononucleated cells, but evolution this important process is unknown. We investigated evolutionary origins function membrane-coalescing agents Myomaker Myomixer in various groups chordates. Here, we report that likely arose through gene duplication last common ancestor tunicates vertebrates, while appears have evolved de novo early vertebrates. Functional tests revealed a complex history...
Muscle precursor cells known as myoblasts are essential for muscle development and regeneration. Notch signaling is an ancient intercellular communication mechanism that plays prominent roles in controlling the myogenic program of myoblasts. Currently whether how cues feedback to refine activities these largely unknown. Here, by mouse human gene gain/loss-of-function studies, we report MyoD directly turns on expression Notch-ligand Dll1 which activates pathway prevent precautious...
ABSTRACT Vertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), drives myoblast fusion muscle multinucleation. Yet they divergent in when where express Mymk. In vertebrates, all developing skeletal muscles Mymk obligately multinucleated. tunicates, is expressed only post-metamorphic multinucleated muscles, but absent from mononucleated larval muscles. this study, we demonstrate cis-regulatory sequence differences the promoter region of underlie...
The prevalence of obesity has risen to an unprecedented level. According World Health Organization, over 500 million adults, equivalent 10%-14% the world population, were obese with a body mass index (BMI) 30 kg/m(2) or greater in 2008.(1) This rising and earlier onset is believed be resulted from interplay genetic factors, over-nutrition physical inactivity modern lifestyles. Obesity also increases susceptibility metabolic syndromes, hypertension, cardiovascular diseases, Type 2 diabetes...
The Cre/ loxP system is a powerful tool for gene function study in vivo. Regulated expression of Cre recombinase mediates precise deletion genetic elements spatially– and temporally–controlled manner. Despite the robustness this system, it requires great amount effort to create conditional knockout model each individual interest where two sites must be simultaneously inserted cis . current undertaking involves labor-intensive embryonic stem (ES) cell–based targeting tedious...