Single Nuclei RNA Sequencing of the Gastrocnemius Muscle Reveals Unique Transcriptomic Signatures of Peripheral Artery Disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA978497 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study examines the transcriptional profile at the single-nuclei resolution human gastrocnemius skeletal muscle from 20 patients with Peripheral artery disease (PAD) and 12 non-PAD controls. In all libraries, muscle specimens were pooled prior to nuclei isolations were performed.
2023-10-10 | GSE233882 | GEO
Project description:BackgroundLower extremity peripheral artery disease (PAD) is a growing epidemic with limited effective treatment options. Here, we provide a single-nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle.MethodsWe obtained gastrocnemius muscle specimens from 20 patients with PAD and 12 non-PAD controls. Nuclei were isolated and single-nuclei RNA-sequencing was performed. The composition of nuclei was characterized by iterative clustering via principal component analysis, differential expression analysis, and the use of known marker genes. Bioinformatics analysis was performed to determine differences in gene expression between PAD and non-PAD nuclei, as well as subsequent analysis of intercellular signaling networks. Additional histological analyses of muscle specimens accompany the single-nuclei RNA-sequencing atlas.ResultsSingle-nuclei RNA-sequencing analysis indicated a fiber type shift with patients with PAD having fewer type I (slow/oxidative) and more type II (fast/glycolytic) myonuclei compared with non-PAD, which was confirmed using immunostaining of muscle specimens. Myonuclei from PAD displayed global upregulation of genes involved in stress response, autophagy, hypoxia, and atrophy. Subclustering of myonuclei also identified populations that were unique to PAD muscle characterized by metabolic dysregulation. PAD muscles also displayed unique transcriptional profiles and increased diversity of transcriptomes in muscle stem cells, regenerating myonuclei, and fibro-adipogenic progenitor cells. Analysis of intercellular communication networks revealed fibro-adipogenic progenitors as a major signaling hub in PAD muscle, as well as deficiencies in angiogenic and bone morphogenetic protein signaling which may contribute to poor limb function in PAD.ConclusionsThis reference single-nuclei RNA-sequencing atlas provides a comprehensive analysis of the cell composition, transcriptional signature, and intercellular communication pathways that are altered in the PAD condition.
| S-EPMC10599805 | biostudies-literature
Project description:Dysregulated Genes, Biological pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A preliminary analysis
| PRJNA753866 | ENA
Project description:Skeletal muscle is composed of multinucleated myofibers, in which nuclei share the cytoplasm, and other cell types. Here, we performed single-nucleus RNA sequencing (snRNA-Seq) to determine the gene expressions in each nucleus in gastrocnemius and plantaris muscles collected from 12-week-old C57BL/6 wild-type mice. Our datasets also provided a basis for comparing gene expressions between myofibers and other cell types and discovering the novel cell populations in muscle tissues.
2022-01-07 | GSE185678 | GEO
Project description:Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.
| S-EPMC10997596 | biostudies-literature
Project description:Peripheral Artery Disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to acute and chronic ischemia is urgently needed to improve therapeutic options. The aim of this study is understanding miR-210 regulation and role in a mouse model of hindlimb ischemia. To investigate miR-210 function, mice were injected with a miR-210 complementary LNA-oligonucleotide (anti-miR-210). Then, the left femoral artery was dissected in order to induce unilateral hindlimb ischemia. Mice were sacrified 3 days later and gene expression profiles of gastrocnemius muscles were obatained.
2015-10-23 | E-GEOD-43340 | biostudies-arrayexpress
Project description:Identification of novel pathophysiological mechanisms of carotid artery disease at systemic level by studying the gene expression profile of peripheral blood of affected patients with respect to control subjects.
2009-06-30 | E-MEXP-2113 | biostudies-arrayexpress
Project description:Few studies have investigated heterogeneity of selection response in replicate lines subjected to equivalent selection. We developed 4 replicate lines of mice based on high levels of voluntary wheel running (high runner or HR lines) while also maintaining 4 non-selected control lines. This led to the unexpected discovery of the HR mini-muscle (HRmini) phenotype, recognized by a 50% reduction in hindlimb muscle mass, which became fixed in 1 of the 4 HR selected lines. Here, we report genome-wide expression profiling describing transcriptome differences between HRnormal and HRmini medial gastrocnemius. This work provides a resource for understanding differences in muscle phenotypes in populations exhibiting high running capacity. Male mice were used from an animal model of 4 closed lines selectively bred for high voluntary wheel-running behaviour (HR) and 4 control lines bred without intentional selection, described in Swallow et al. Animals used in the current work were sampled from generation 37 at a mean age of 84 days (range = 79-86). For microarray analysis, we used gastrocnemius muscles (including both lateral and medial portions) from HRmini line #3 and HRnormal line #8 (n = 6, in each group). To obtain sufficient RNA, gastrocnemius samples of HRmini were pooled from left and right limbs from each animal, whereas HRnormal gastrocnemius was sampled from either left or right limb only.
2013-02-19 | E-GEOD-41910 | biostudies-arrayexpress
Project description:microRNA counts from gastrocnemius medialis (ENCSR505IZZ)
| PRJNA909704 | ENA
Project description:microRNA counts from gastrocnemius medialis (ENCSR655NLY)
| PRJNA909660 | ENA