Single Nuclei RNA Sequencing of the Gastrocnemius Muscle Reveals Unique Transcriptomic Signatures of Peripheral Artery Disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233882 | GEO | 2023/10/10
REPOSITORIES: GEO
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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 patients with both PAD and Chronic Kidney Disease (CKD). In all libraries, muscle specimens were pooled prior to nuclei isolations were performed.
2025-02-26 | GSE284482 | GEO
Project description:Single Nuclei RNA Sequencing of the Gastrocnemius Muscle Reveals Unique Transcriptomic Signatures of Peripheral Artery Disease
| PRJNA978497 | ENA
Project description:This study examines the transcriptional profile at a single-nuclei resolution in mice with muscle-specific deletion of the aryl hydrocarbon receptor (AHR). Wildtype (AHRfl/fl, floxed Cre negative littermates) and AHRmKO (AHR muscle specific knockout) mice were given chronic kidney disease via adenine supplemented diet. Mice were then subjected to femoral artery ligation as an experimental model of peripheral artery disease. Tibialis anterior muscles were harvested at five days post-surgery and immediately snap frozen in liquid nitrogen and stored at -80C until nuclei isolation. In both libraries, muscle specimens were pooled from three males prior to nuclei isolations were performed.
2023-06-08 | GSE217751 | GEO
Project description:Background Peripheral artery disease (PAD) is caused by atherosclerosis and chronic narrowing of lower limb arteries leading to decreased muscle perfusion and oxygenation. Current guidelines for treating PAD include endovascular strategies or bypass surgery but long-term outcomes have been suboptimal. This is likely due to our limited understanding of the contribution of the microvasculature as well as other cell types, in particular macrophages, to PAD skeletal muscle pathophysiology. We used single cell sequencing to investigate cellular and transcriptional heterogeneity of the skeletal muscle microenvironment in PAD. Methods Samples from the medial head of the gastrocnemius muscle of individuals undergoing either lower limb aneurysm surgery (controls) or PAD bypass surgery (PAD) were collected. Samples were either frozen for histological evaluation (control: n=4; PAD: n=6) or were immediately processed for single cell RNA sequencing of mononuclear cells (control: n=4; PAD: n= 4). Bioinformatic tools were used to annotate cell types and their subpopulations, to study transcriptional changes and to analyze cellular interactions. Results We generated a dataset comprised of 106,566 high-quality, deep-sequenced cells that compose the muscle microenvironment. Focusing on endothelial cells (ECs) and macrophages, we confirmed the presence of ATF3/4+ ECs with angiogenic and immune regulatory capacities in human muscle and found that their transcriptional profile profoundly alters during PAD. Also, capillary ECs display features of endothelial to mesenchymal transition. Furthermore, we identified LYVE1hiMHCIIlow resident macrophages as the dominant macrophage population in human muscle, even under a chronic inflammatory condition such as PAD. During PAD, LYVE1hiMHCIIlow macrophages get activated and acquire a more pro-inflammatory profile. Finally, we map strong intercellular communication in the muscle microenvironment, which is significantly altered in PAD. Conclusions The dataset we present here provides a highly valuable resource for gaining deeper insights into the critical roles that cells in the muscle microenvironment may play in PAD skeletal muscle pathology. We propose that targeting the crosstalk between ECs and macrophages could provide novel insights for developing effective treatments against this disease.
2025-04-08 | GSE287300 | GEO
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:Gastrocnemius muscle biopsies were obtained from 15 health older adults without peripheral artery disease (PAD), 20 PAD patients with intermittent claudication, and 16 patients with critical limb ischemia undergoing limb amputation. Gene expression analysis was performed using RNA sequencing analysis.
2018-11-30 | GSE120642 | 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:In recent years, thanks to the great development of mass spectrometry (MS)-based high-throughput proteomic techniques, a large-scale protein characterization is less challenging. Proteomic approaches have been successfully applied to SM in different experimental models [21–24]; however, to date, there is little information on ECM proteins and how they change during ageing. The identification and quantification of ECM components and their interactions are es-sential steps to understand the role of the matrisome in sarcopenia. In this context, we combined a proteomic approach (i.e., LC-MS/MS and bioinformatic analyses) with mor-phological and morphometrical evaluations at fluorescence and transmission electron microscopy of the gastrocnemius muscle in adult and old mice. This age range has been selected since it has been observed that most of changes in muscle protein expression take place after middle age. The gastrocnemius muscle was selected for analysis since it is prevalently composed of fast-twitch fibre, which are especially affected by atrophy during aging. Our findings highlighted several modifications of ECM protein composition and organization in old mice, which likely play a role in the alteration of muscle properties during aging.
2022-02-17 | PXD027895 | Pride
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:We report the differentially expressed genes among people with PAD Progression, PAD no progression compared to non-PAD.
2023-03-14 | GSE181930 | GEO