Lineage tracing of nuclei in skeletal myofibers uncovers distinct transcripts and interplay between myonuclear populations.

Multinucleated skeletal muscle cells need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in cells that already harbor hundreds of nuclei. Here we utilize nuclear RNA-sequencing approaches and develop a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei.

Temporal regulation of the Mediator complex during muscle proliferation, differentiation, regeneration, aging, and disease.

Genesis of skeletal muscle relies on the differentiation and fusion of mono-nucleated muscle progenitor cells into the multi-nucleated muscle fiber syncytium. The temporally-controlled cellular and morphogenetic changes underlying this process are initiated by a series of highly coordinated transcription programs. At the core, the myogenic differentiation cascade is driven by muscle-specific transcription factors, i.

YTHDF2 governs muscle size through a targeted modulation of proteostasis.

The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-β pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear.

Lineage tracing of newly accrued nuclei in skeletal myofibers uncovers distinct transcripts and interplay between nuclear populations.

Multinucleated skeletal muscle cells have an obligatory need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in syncytial cells that already harbor hundreds of nuclei. To begin to answer this long-standing question, we utilized nuclear RNA-sequencing approaches and developed a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei.

Molecular regulation of satellite cells via intercellular signaling.

Somatic stem cells are tissue-specific reserve cells tasked to sustain tissue homeostasis in adulthood and/or effect tissue regeneration after traumatic injury. The stem cells of skeletal muscle tissue are the satellite cells, which were originally described and named after their localization beneath the muscle fiber lamina and attached to the multi-nucleated muscle fibers. During adult homeostasis, satellite cells are maintained in quiescence, a state of reversible cell cycle arrest.

A Tead1-Apelin axis directs paracrine communication from myogenic to endothelial cells in skeletal muscle.

Apelin (Apln) is a myokine that regulates skeletal muscle plasticity and metabolism and declines during aging. Through a yeast one-hybrid transcription factor binding screen, we identified the TEA domain transcription factor 1 (Tead1) as a novel regulator of the promoter. Single-cell analysis of regenerating muscle revealed that the apelin receptor () is enriched in endothelial cells, whereas is enriched in myogenic cells.

Fibroblast growth factor 6 regulates sizing of the muscle stem cell pool.

Skeletal muscle stem cells, i.e., satellite cells (SCs), are the essential source of new myonuclei for skeletal muscle regeneration following injury or chronic degenerative myopathies.

Deficiency of Axl aggravates pulmonary arterial hypertension via BMPR2.

Pulmonary arterial hypertension (PAH), is a fatal disease characterized by a pseudo-malignant phenotype. We investigated the expression and the role of the receptor tyrosine kinase Axl in experimental (i.e.

Myf6/MRF4 is a myogenic niche regulator required for the maintenance of the muscle stem cell pool.

The function and maintenance of muscle stem cells (MuSCs) are tightly regulated by signals originating from their niche environment. Skeletal myofibers are a principle component of the MuSC niche and are in direct contact with the muscle stem cells. Here, we show that Myf6 establishes a ligand/receptor interaction between muscle stem cells and their associated muscle fibers.

Muscle stem cell renewal suppressed by Gas1 can be reversed by GDNF in mice.

Muscle undergoes progressive weakening and regenerative dysfunction with age due in part to the functional decline of skeletal muscle stem cells (MuSCs). MuSCs are heterogeneous but whether their gene expression changes with age and the implication of such changes are unclear. Here we show that in mice, Growth arrest-specific gene 1 (Gas1) is expressed in a small subset of young MuSCs with its expression progressively increasing in larger fractions of MuSCs later in life.

Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study.

Background: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients.

Effects of Pressure and pH on the Physical Stability of an I-Motif DNA Structure.

The thermodynamic stability of a cytosine(C)-rich i-motif tract of DNA, which features pH-sensitive [C..H.

Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.

Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood.

Manipulating and quantifying spin states in solution as a function of pressure and temperature.

Monitoring the spin states of species in solution is a crucial aspect of understanding magnetic properties as well as spin-labile sensing, supramolecular, catalytic and biochemical processes. Herein, we describe the first quantitative variable-pressure and variable-temperature method of determining spin states in solution, demonstrate that it is accurate, and identify a simultaneous T and P sensor system.

Effects of Pressure and pH on the Hydrolysis of Cytosine: Implications for Nucleotide Stability around Deep-Sea Black Smokers.

The relatively low chemical stability of cytosine compared with other nucleobases is a key concern in origin-of-life scenarios, but the effect of pressure on the rate of hydrolysis of cytosine to uracil remains unknown. Through in situ NMR spectroscopy measurements, it has been determined that the half-life of cytosine at 373.15 K decreases from (18.

Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency.

When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic 'scaling' of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.

β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair.

Skeletal muscle regeneration relies on a pool of resident muscle stem cells called satellite cells (MuSCs). Following injury-induced destruction of the myofibers, quiescent MuSCs are activated and generate transient amplifying progenitors (myoblasts) that will fuse to form new myofibers. Here, we focus on the canonical Wnt signaling pathway and find that either conditional β-catenin disruption or activation in adult MuSCs results in perturbation of muscle regeneration.

A series of Cre-ER(T2) drivers for manipulation of the skeletal muscle lineage.

We report the generation of five mouse strains with the tamoxifen-inducible Cre (Cre-ER(T) (2) ; CE) gene cassette knocked into the endogenous loci of Pax3, Myod1, Myog, Myf6, and Myl1, collectively as a resource for the skeletal muscle research community. We characterized these CE strains using the Cre reporter mice, R26R(L) (acZ) , during embryogenesis and show that they direct tightly controlled tamoxifen-inducible reporter expression within the expected cell lineage determined by each myogenic gene. We also examined a few selected adult skeletal muscle groups for tamoxifen-inducible reporter expression.

A novel finding: the effect of nurse practitioners on the relation to quality of life, anxiety, and depressive symptoms in vascular surgery.

Background: An increasing number of vascular surgery units expand their team with nurse practitioners (NPs) to optimize patient care. There are no previously performed studies which assessed the influence of NPs on patients' quality of life (QoL), anxiety, and depressive symptom levels. The transition in care from surgeon to NP in the vascular surgery unit of our hospital facilitated the comparison of both groups.

Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) and MyoD(+) myogenic progenitors by expressing oncogenic Kras(G12D) and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS.

Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells.

Skeletal muscle contains Pax7-expressing muscle stem or satellite cells, enabling muscle regeneration throughout most of adult life. Here, we demonstrate that induced inactivation of Pax7 in Pax7-expressing cells of adult mice leads to loss of muscle stem cells and reduced heterochromatin condensation in rare surviving satellite cells. Inactivation of Pax7 in Myf5-expressing cells revealed that the majority of adult muscle stem cells originate from myogenic lineages, which express the myogenic regulators Myf5 or MyoD.

The satellite cell builds its nest under Notch's guidance.

Recently in Developmental Cell, Bröhl et al. (2012) reported that Notch regulates muscle stem cell homing to its niche. Notch is required when myogenic cells cease producing new fibers and become sequestered between a newly forming basement membrane and the muscle fiber surface: the position that defines them as satellite cells.