Circadian Dysfunction in Skeletal Muscle Impairs Limb Perfusion and Muscle Regeneration in Peripheral Artery Disease [Myotube-ATACseq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1153520 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30463008_1.fastq.gz | Fastqsanger.gz | |||
| SRR30463008_2.fastq.gz | Fastqsanger.gz | |||
| SRR30463009_1.fastq.gz | Fastqsanger.gz | |||
| SRR30463009_2.fastq.gz | Fastqsanger.gz | |||
| SRR30463010_1.fastq.gz | Fastqsanger.gz |
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Project description:Peripheral arterial disease (PAD), caused by atherosclerosis, leads to limb ischemia, muscle damage, and impaired mobility in the lower extremities. Recent studies suggest that circadian rhythm disruptions can hinder vascular repair during ischemia, but the specific tissues involved and the impact on muscle health remain unclear. This study investigates the role of the skeletal muscle circadian clock in muscle adaptation to ischemic stress using a surgical mouse model of hindlimb ischemia. We used mice with specific genetic loss of the circadian clock activator, BMAL1, in adult skeletal muscle tissues (Bmal1muscle). Bmal1muscle mice and controls underwent femoral artery ligation surgery to induce hindlimb ischemia. Laser doppler imaging was used to assess limb perfusion at various time points after the surgery. Muscle tissues were analyzed with RNA sequencing and histological examination to investigate PAD-related muscle pathologies. Additionally, we studied the role of BMAL1 in muscle fiber adaptation to hypoxia using RNA and ATAC sequencing analyses in primary myotube culture model. Disrupted expression of circadian rhythm-related genes was observed in existing RNA-seq datasets from PAD patient-derived endothelial cells and ischemic limb skeletal muscles. Genetic loss of Bmal1 specifically in adult mouse skeletal muscle tissues delayed reperfusion recovery following induction of hindlimb ischemia. Histological examination of muscle tissues showed reduced regenerated myofiber number and a decreased proportion of type IIB fast-twitch myofibers in Bmal1musc mouse muscles in the ischemic limbs, but not in their contralateral non-ischemic limbs. Transcriptomic analysis revealed abrogated metabolic, angiogenic, and myogenic pathways relevant to hypoxia-adaptation in Bmal1musc mouse muscles. These changes were corroborated in Bmal1-deficient cultured primary myotubes cultured under hypoxic conditions.
2024-09-02 | GSE275893 | GEO
Project description:Peripheral arterial disease (PAD), caused by atherosclerosis, leads to limb ischemia, muscle damage, and impaired mobility in the lower extremities. Recent studies suggest that circadian rhythm disruptions can hinder vascular repair during ischemia, but the specific tissues involved and the impact on muscle health remain unclear. This study investigates the role of the skeletal muscle circadian clock in muscle adaptation to ischemic stress using a surgical mouse model of hindlimb ischemia. We used mice with specific genetic loss of the circadian clock activator, BMAL1, in adult skeletal muscle tissues (Bmal1muscle). Bmal1muscle mice and controls underwent femoral artery ligation surgery to induce hindlimb ischemia. Laser doppler imaging was used to assess limb perfusion at various time points after the surgery. Muscle tissues were analyzed with RNA sequencing and histological examination to investigate PAD-related muscle pathologies. Additionally, we studied the role of BMAL1 in muscle fiber adaptation to hypoxia using RNA and ATAC sequencing analyses in primary myotube culture model. Disrupted expression of circadian rhythm-related genes was observed in existing RNA-seq datasets from PAD patient-derived endothelial cells and ischemic limb skeletal muscles. Genetic loss of Bmal1 specifically in adult mouse skeletal muscle tissues delayed reperfusion recovery following induction of hindlimb ischemia. Histological examination of muscle tissues showed reduced regenerated myofiber number and a decreased proportion of type IIB fast-twitch myofibers in Bmal1musc mouse muscles in the ischemic limbs, but not in their contralateral non-ischemic limbs. Transcriptomic analysis revealed abrogated metabolic, angiogenic, and myogenic pathways relevant to hypoxia-adaptation in Bmal1musc mouse muscles. These changes were corroborated in Bmal1-deficient cultured primary myotubes cultured under hypoxic conditions.
2024-09-01 | GSE275812 | GEO
Project description:Circadian Dysfunction in Skeletal Muscle Impairs Limb Perfusion and Muscle Regeneration in Peripheral Artery Disease [Myotube-RNAseq]
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Project description:Peripheral arterial disease (PAD), caused by atherosclerosis, leads to limb ischemia, muscle damage, and impaired mobility in the lower extremities. Recent studies suggest that circadian rhythm disruptions can hinder vascular repair during ischemia, but the specific tissues involved and the impact on muscle health remain unclear. This study investigates the role of the skeletal muscle circadian clock in muscle adaptation to ischemic stress using a surgical mouse model of hindlimb ischemia. We used mice with specific genetic loss of the circadian clock activator, BMAL1, in adult skeletal muscle tissues (Bmal1muscle). Bmal1muscle mice and controls underwent femoral artery ligation surgery to induce hindlimb ischemia. Laser doppler imaging was used to assess limb perfusion at various time points after the surgery. Muscle tissues were analyzed with RNA sequencing and histological examination to investigate PAD-related muscle pathologies. Additionally, we studied the role of BMAL1 in muscle fiber adaptation to hypoxia using RNA and ATAC sequencing analyses in primary myotube culture model. Disrupted expression of circadian rhythm-related genes was observed in existing RNA-seq datasets from PAD patient-derived endothelial cells and ischemic limb skeletal muscles. Genetic loss of Bmal1 specifically in adult mouse skeletal muscle tissues delayed reperfusion recovery following induction of hindlimb ischemia. Histological examination of muscle tissues showed reduced regenerated myofiber number and a decreased proportion of type IIB fast-twitch myofibers in Bmal1musc mouse muscles in the ischemic limbs, but not in their contralateral non-ischemic limbs. Transcriptomic analysis revealed abrogated metabolic, angiogenic, and myogenic pathways relevant to hypoxia-adaptation in Bmal1musc mouse muscles. These changes were corroborated in Bmal1-deficient cultured primary myotubes cultured under hypoxic conditions.
2024-09-01 | GSE275811 | GEO
Project description:Circadian Dysfunction in Skeletal Muscle Impairs Limb Perfusion and Muscle Regeneration in Peripheral Artery Disease
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Project description:Arrestin Domain Containing 2 and 3 (Arrdc2/3) are genes whose mRNA contents are decreased in young skeletal muscle following mechanical overload. Arrdc3 is linked to the regulation of signaling pathways in non-muscle cells that could influence skeletal muscle size. Despite a similar amino acid sequence, Arrdc2 function remains undefined. The purpose of this study was to further explore the relationship of Arrdc2/Arrdc3 expression with changes in mechanical load in young and aged muscle and define the effect of Arrdc2/3 expression on myotube diameter. In young and aged mice, mechanical load was decreased using hindlimb suspension while mechanical load was increased by reloading previously unloaded muscle or inducing high force contractions. Arrdc2 and Arrdc3 mRNAs were overexpressed in C2C12 myotubes using adenoviruses. Myotube diameter was determined 48 h post-transfection and RNA sequencing was performed on those samples. Arrdc2 and Arrdc3 mRNA content was higher in the unloaded muscle within 1 day of disuse and remained higher up through 10 days. The induction of Arrdc2 mRNA was more pronounced in aged muscle than young muscle in response to unloading. Reloading previously unloaded muscle of young and aged mice restored Arrdc2 and Arrdc3 levels to ambulatory levels. Increasing mechanical load beyond normal ambulatory levels lowered Arrdc2 but not Arrdc3 mRNA in young and aged muscle. Arrdc2, not Arrdc3, overexpression was sufficient to lower myotube diameter in C2C12 cells in part by altering the transcriptome favoring muscle atrophy. These data are consistent with Arrdc2 contributing to disuse atrophy, particularly in aged muscle.
2024-01-23 | GSE248869 | GEO
Project description:Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. During the early development, a pool of skeletal stem cells (SSCs) proliferates and then diverge into either myoblast. Myoblast further fusion and develop into myotube. However, the landscape from muscle stem cells to myotubes in goats is not yet clear. This study aims to characterize the changes in the expression profile of skeletal muscle stem cells that differentiate into myoblasts, then migrate and fuse to form myotubes.
2021-11-11 | PXD029693 |
Project description:Epigenomic and transcriptomic changes associate with skeletal muscle stem cells to myotube differentiation.
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Project description:Skeletal muscle atrophy is dictated by the balance between protein synthesis and protein breakdown, known as proteostasis. With advanced age, muscle atrophy contributes to development of co-morbidities, loss of strength and independence, and all-cause mortality. Aging also coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence associated secretory phenotype. Previously, we found that a metformin + leucine (MET+LEU) combination treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy. Therefore, the objective of this study was to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence. C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during serum-deprivation (SD) atrophy. Single myofibers were isolated from aged (22-23 mo) C57Bl6/J mice, and human primary myoblasts were extracted from a healthy older adult donor. 25 + 125 µM MET+LEU treatment increased differentiation of myotubes and prevented SD induced atrophy. Low concentration (0.1 + 0.5 µM) MET+LEU had unique effects to prevent myotube atrophy and cause transcriptional reprogramming compared to individual therapies. SD increased inflammatory and cellular senescence pathways that was reversed with MET+LEU treatment. SD resulted in dysregulated proteostasis that was rescued with MET+LEU, and proteasome inhibition with MG-132 also rescued myotube atrophy. Cellular senescence transcriptional pathways and markers increased by SD were reversed with MET+LEU treatment, and dasatinib + quercetin (D+Q) senolytic treatment prevented myotube atrophy similar to MET+LEU. In aged myofibers, MET+LEU prevented SD atrophy, and in human primary myotubes MET+LEU prevented reductions in myonuclei fusion. These data provide evidence that MET+LEU has muscle cell intrinsic properties to prevent atrophy by reversing senescence and improving proteostasis
2023-04-19 | GSE221941 | GEO