Dataset Information

Single-cell transcriptional profiles in human skeletal muscle.

ABSTRACT: Skeletal muscle is a heterogeneous tissue comprised of muscle fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism and cognition. We investigated the gene expression patterns of skeletal muscle cells using RNA-seq of subtype-pooled single human muscle fibers and single cell RNA-seq of mononuclear cells from human vastus lateralis, mouse quadriceps, and mouse diaphragm. We identified 11 human skeletal muscle mononuclear cell types, including two fibro-adipogenic progenitor (FAP) cell subtypes. The human FBN1+ FAP cell subtype is novel and a corresponding FBN1+ FAP cell type was also found in single cell RNA-seq analysis in mouse. Transcriptome exercise studies using bulk tissue analysis do not resolve changes in individual cell-type proportion or gene expression. The cell-type gene signatures provide the means to use computational methods to identify cell-type level changes in bulk studies. As an example, we analyzed public transcriptome data from an exercise training study and revealed significant changes in specific mononuclear cell-type proportions related to age, sex, acute exercise and training. Our single-cell expression map of skeletal muscle cell types will further the understanding of the diverse effects of exercise and the pathophysiology of muscle disease.

SUBMITTER: Rubenstein AB

PROVIDER: S-EPMC6959232 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Single-cell transcriptional profiles in human skeletal muscle.

Rubenstein Aliza B AB Smith Gregory R GR Raue Ulrika U Begue Gwénaëlle G Minchev Kiril K Ruf-Zamojski Frederique F Nair Venugopalan D VD Nair Venugopalan D VD Wang Xingyu X Zhou Lan L Zaslavsky Elena E Trappe Todd A TA Trappe Scott S Sealfon Stuart C SC

Scientific reports 20200114 1

Skeletal muscle is a heterogeneous tissue comprised of muscle fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism and cognition. We investigated the gene expression patterns of skeletal muscle cells using RNA-seq of subtype-pooled single human muscle fibers and single cell RNA-seq of mononuclear cells from human vastus lateralis, mouse quadriceps, and mouse diaphragm. We identified 11 human skeletal muscle mononuclear cell types, including two fibro-ad ...[more]

PMID: 31937892

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Project description:Development of the white striping (WS) abnormality adversely impacts overall quality of broiler breast meat. Its etiology remains unclear. This study aimed at exploring transcriptional profiles of broiler skeletal muscles exhibiting different WS severity to elucidate molecular mechanisms underlying the development and progression of WS. Total RNA was isolated from pectoralis major of male 7-week-old Ross 308 broilers. The samples were classified as mild (n = 6), moderate (n = 6), or severe (n = 4), based on number and thickness of the white striations on the meat surface. The transcriptome was profiled using a chicken gene expression microarray with one-color hybridization technique. Gene expression patterns of each WS severity level were compared against each other; hence, there were three comparisons: moderate vs. mild (C1), severe vs. moderate (C2), and severe vs. mild (C3). Differentially expressed genes (DEGs) were identified using the combined criteria of false discovery rate ≤ 0.05 and absolute fold change ≥1.2. Differential expression of 91, 136, and 294 transcripts were identified in C1, C2, and C3, respectively. There were no DEGs in common among the three comparisons. Based on pathway analysis, the enriched pathways of C1 were related with impaired homeostasis of macronutrients and small biochemical molecules with disrupted Ca2+-related pathways. Decreased abundance of the period circadian regulator suggested the shifted circadian phase when moderate WS developed. The enriched pathways uniquely obtained in C2 were RNA degradation, Ras signaling, cellular senescence, axon guidance, and salivary secretion. The DEGs identified in those pathways might play crucial roles in regulating cellular ion balances and cell-cycle arrest. In C3, the pathways responsible for phosphatidylinositol 3-kinase-Akt signaling, p53 activation, apoptosis, and hypoxia-induced processes were modified. Additionally, pathways associated with a variety of diseases with the DEGs involved in regulation of [Ca2+], collagen formation, microtubule-based motor, and immune response were identified. Eight pathways were common to all three comparisons (i.e., calcium signaling, Ras-associated protein 1 signaling, ubiquitin-mediated proteolysis, vascular smooth muscle contraction, oxytocin signaling, and pathway in cancer). The current findings support the role of intracellular ion imbalance, particularly Ca2+, oxidative stress, and impaired programmed cell death on WS progression.

Project description:Background:Human immunodeficiency virus (HIV)-infected individuals are at increased risk of age-associated functional impairment, even with effective antiretroviral therapy (ART). A concurrent characterization of skeletal muscle, physical function, and immune phenotype in aviremic middle-aged HIV-infected adults represents a knowledge gap in prognostic biomarker discovery. Methods:We undertook a prospective observational study of 170 middle-aged, HIV-infected ambulatory men and women with CD4+ T-cell counts of at least 350/µL and undetectable plasma viremia while on effective ART, and uninfected control participants. We measured biomarkers for inflammation and immune activation, fatigue, the Veterans Aging Cohort Study mortality index, and physical function. A subset also received a skeletal muscle biopsy and computed tomography scan. Results:Compared to the uninfected participants, HIV-infected participants displayed increased immune activation (P < .001), inflammation (P = .001), and fatigue (P = .010), and in a regression model adjusting for age and sex displayed deficits in stair-climb power (P < .001), gait speed (P = .036), and predicted metabolic equivalents (P = .019). Skeletal muscle displayed reduced nuclear peroxisome proliferator-activated receptor-γ coactivator 1α-positive myonuclei (P = .006), and increased internalized myonuclei (P < .001) that correlated with immune activation (P = .003) and leukocyte infiltration (P < .001). Internalized myonuclei improved a model for HIV discrimination, increasing the C-statistic from 0.84 to 0.90. Conclusions:Asymptomatic HIV-infected middle-aged adults display atypical skeletal muscle profiles, subclinical deficits in physical function, and persistent inflammation and immune activation. Identifying biomarker profiles for muscle dysregulation and risk for future functional decline in the HIV-infected population will be key to developing and monitoring preventive interventions. Clinical Trials Registration:NCT03011957.

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Single-cell transcriptional profiles in human skeletal muscle.

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Single-cell transcriptional profiles in human skeletal muscle.

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