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Biology subjects

Serrano, N.

Publications and source records attributed to Serrano, N..

6 recordsLinked to original sources

Exercise preconditioning confers skeletal muscle myometaplasticity

Previously exercise trained skeletal muscle is more growth-responsive to retraining. Using a murine training-detraining-retraining approach and multi-omics, we find that Pecam1 gene expression is lower, but capillarization is appreciably higher in previously trained (preconditioned) relative to naive trained control muscle. Greater capillarity could be permissive for accelerated hypertrophic adaptation. Exercise preconditioned myonuclei feature differential promoter CpG regulation in genes related to Wnt signaling. These epigenetic alterations with retraining align with our prior observations of methylation changes within the same pathway after a longer period of chronic training, suggesting a more rapid response due to preconditioning. Methylome-transcriptome integration and single myonucleus RNA-sequencing expose the polyamine metabolism enzyme Smox as a target that relates to heightened hypertrophic adaptability with retraining. Smox induction is sufficient to cause hypertrophy in aligned myotubes cultured on a stiffness-tuned substrate along with a growth-supportive transcriptional program. Integration of our multi-omics data suggests that Smox regulates repression of Ddit4/Redd1 (an inhibitor of mTORC1 signaling) after retraining. Smox may govern a favorable muscle fiber growth environment in previously trained muscle by sensitizing anabolic potential through polyamine metabolism. A lower adaptive threshold mediated by Smox could contribute to myometaplasticity, or a change to how subsequent muscle adaptations are made.

molecular biology↗

Transient MYC Mimicking the Exercise Response Orchestrates Multifaceted Skeletal Muscle Adaptations

Despite decades of study, MYCs physiological role in adult tissues remains obscured by the models used to investigate it. Most work relies almost exclusively on chronic or constitutive MYC induction that recapitulates the sustained activity found in tumorigenesis and expectedly produces pathological outcomes. What has gone largely untested is how MYC operates when induced in a controlled and physiologically relevant manner, as it is during adaptive processes such as exercise. Using a recombination-independent strategy in adult skeletal muscle, transient MYC bursts drive coordinated hypertrophic-metabolic reprogramming followed by a shift in myosin fiber type, recapitulating adaptations characteristic of concurrent endurance and resistance training. A single pleiotropic transcription factor governing several aspects of muscle health reframes perspectives on a gene understood almost entirely in the context of pathology. We uncover a previously unrecognized muscle-specific role for MYC in controlling muscle cell composition and present a multi-timepoint multi-omic resource for interrogating MYC: data.myoanalytics.com/study/myc_transient/gene.

Cell Biology↗

Myonuclear Dynamics After Skeletal Muscle Surgical Injury

A hallmark of damaged skeletal muscle fibers is displaced myonuclei that are no longer peripherally positioned. Displaced myonuclei are dogmatically thought to be derived exclusively from muscle stem cell (satellite cell) fusion. Using a surgical resection muscle injury model and in vivo recombination-independent resident myonuclear labeling, we detail the prevalence, time course, and origin of displaced myonuclei in response to a non-chemically-mediated muscle trauma. We found that: 1) non-satellite cell-derived (resident) displaced myonuclei emerge seven days after surgical injury in similar proportion to exogenous (satellite cell-derived) displaced myonuclei in intact muscle fibers, with a biased prevalence in myosin heavy chain IIB muscle fibers, 2) muscle fibers with multiple ([≥]2) displaced resident myonuclei was an unexpected but noteworthy feature of muscle fibers 7 days after injury, 3) embryonic myosin-expressing fibers at seven days post-surgery expectedly contain predominantly satellite-cell derived displaced myonuclei, but a subset have displaced resident myonuclei, and 4) satellite cell numbers in intact muscle do not increase until 7 days post-surgery. These data may help inform whether to target satellite cell-initiated processes, myonuclear-initiated processes, or both to facilitate muscle fiber injury repair. This information could lead to more effective therapeutic strategies for treating muscle trauma.

cell biology↗

Displaced myonuclei are attributable to both resident myonuclear migration and stem cell fusion during mechanical loading in adult skeletal muscle

Non-peripheral myonuclei are characteristic of skeletal muscle pathology and severe injury but also appear after exercise and with aging. Displaced myonuclei are typically attributed to the activity of muscle stem cells, or satellite cells. We sought to address whether displaced myonuclei in adult skeletal muscle are exclusively from an exogenous source such as satellite cells or can result from resident myonuclear migration. To address this question, we used a murine recombination-independent muscle fibre-specific doxycycline-inducible fluorescent myonuclear labelling approach, EdU stem cell fate tracking, two durations of muscle mechanical overload (MOV, 3 days and 7 days), and fluorescent histology. Our findings show that: 1) displaced myonuclei emerge early during MOV, 2) resident myonuclear movement occurs rapidly during MOV, and 3) the contribution of resident versus exogenous displaced myonuclei depends on MOV duration, fibre type, and fibre size. These observations provide fundamental insights on myonuclear motility in response to stress in vivo and reframe our understanding of how a recognized feature of mammalian skeletal muscle can emerge in response to mechanical loading. SummaryRecombination-independent muscle fibre-specific doxycycline-inducible fluorescent myonuclear labelling in adult mice unambiguously reveals how resident myonuclei relocate rapidly during stress and contribute to the appearance of displaced myonuclei.

cell biology↗

Chitosan stimulates root hair callose deposition and inhibits root hair growth

Although angiosperm plants have a general capacity to react after the immunity elicitor chitin or chitosan treatment by the cell wall callose deposition, this response in particular cell types and its evolutionary conservation is not understood. Here we show that also the growing root hairs (RHs) of Arabidopsis can respond to a mild (0.001%) chitosan treatment by the callose deposition and by a deceleration of the RH growth. We demonstrate that the glucan synthase-like 5 (GSL5)/PMR4 is vital for chitosan-induced callose deposition but not for RH growth inhibition. Upon the higher chitosan concentration (0.01%) treatment, RHs do not deposit callose, while growth inhibition is prominent. To understand the specificities of the low and high concentration chitosan treatments, we analysed the corresponding PTI signalling components, gene expression, and RH cellular endomembrane and cytoskeleton modifications. Importantly, chitosan-induced callose deposition is also present in the functionally analogous and evolutionarily only distantly related RH-like structures rhizophores (lycophytes) and rhizoids (bryophytes). Our results point to the RH callose deposition as a conserved strategy of soil-anchoring plant cells (rhizoids/rhizophores/RHs) to deal with mild biotic stress. At the same time, high chitosan concentration prominently disturbs intracellular dynamics, tip-localised endomembrane compartments and RH growth, precluding callose deposition.

plant biology↗

Extraordinary Fast-Twitch Fiber Abundance Elite Weightlifters

Human skeletal muscle fibers exist across a continuum of slow [->] fast-twitch. The amount of each fiber type (FT) influences muscle performance but remains largely unexplored in elite athletes, particularly from strength/power sports. To address this nescience, vastus lateralis (VL) biopsies were performed on World/Olympic (female, n=6, \"WCF\") and National-caliber (female, n=9, \"NCF\"; and male, n=6, \"NCM\") American weightlifters. Participant accolades included 3 Olympic Games, 19 World Championships, 25 National records, and >170 National/International medals. Samples were analyzed for myosin heavy chain (MHC) content via SDS-PAGE using two distinct techniques: single fiber (SF) distribution (%) and homogenate (HG) composition. These athletes displayed the highest MHC IIa concentrations ever reported in healthy VL (23{+/-}9% I, 5{+/-}3% I/IIa, 67{+/-}13% IIa, and 6{+/-}10% IIa/IIx), with WCF expressing a notable 71{+/-}17% (NCF=67{+/-}8%, NCM=63{+/-}16%). The heavyweights accounted for 91% of the MHC IIa/IIx fibers. When compared to SF, HG overestimated MHC I (23{+/-}9 vs. 31{+/-}9%) and IIx (0{+/-}0 vs. 3{+/-}6%) by misclassifying I/IIa fibers as I and IIa/IIx fibers as IIx. These findings suggest athlete caliber (World vs. National), training experience, and body mass determine FT% more than sex and refutes the common pronouncement that women possess more slow and fewer fast-twitch fibers than men. Our results also show the abundance of pure MHC IIa and rarity of IIx in elite strength/power-trained athletes, indicate a potential link between MHC IIa/IIx frequency and body mass, and question the fidelity of HG as a measure of FT% distribution. The extreme fast-twitch abundance partially explains how elite weightlifters generate high forces in rapid time-frames. These data highlight the need for more cellular and molecular muscle research on elite anaerobic athletes.

physiology↗