Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers

ABSTRACT: While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the emergence of distinct myonuclear populations in postnatal development and their reactivation in aging muscle. Our datasets also provided a platform for discovery of novel genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.

ORGANISM(S): Mus musculus

PROVIDER: GSE147127 | GEO | 2020/10/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single-nucleus RNA sequencing of gastrocnemius and plantaris muscles.

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

Single nucleus RNA-seq analysis of the TA muscles from WT and Dmd Exon 51 Knockout mice

Project description:Duchenne muscular dystrophy (DMD) is a fatal muscle disorder characterized by cycles of degeneration and regeneration of multinucleated myofibers and pathological activation of a variety of other associated cell types. Here, we describe the creation of a new mouse model of DMD caused by deletion of exon 51 of the dystrophin gene, which represents a prevalent mutation in humans. To understand the transcriptional abnormalities and heterogeneity associated with the nuclei of myofibers, as well as other mononucleated cell types that contribute to DMD disease pathogenesis, we performed single nucleus transcriptomics of skeletal muscle of mice with exon 51 deletion. Our results reveal distinctive and previously unrecognized myonuclear subtypes within dystrophic myofibers and uncover degenerative and regenerative transcriptional pathways underlying DMD pathogenesis. Our findings provide new insights into the molecular underpinnings of DMD, controlled by the transcriptional activity of different types of muscle and nonmuscle nuclei.

2020-11-05 | GSE156497 | GEO

Transcriptome analysis of the TA muscles from WT and Dmd Exon 51 Knockout mice

2020-11-05 | GSE156496 | GEO

Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers

Project description:Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers

| PRJNA613077 | ENA

Lineage tracing of newly accrued nuclei in skeletal myofibers uncovers distinct transcripts and interplay between nuclear populations

Project description:Multinucleated skeletal muscle cells have an obligatory need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in syncytial cells that already harbor hundreds of nuclei. To begin to answer this long-standing question, we utilized nuclear RNA-sequencing approaches and developed a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei. Our findings reveal the presence of conserved markers of newly fused nuclei both during development and after a hypertrophic stimulus in the adult. However, newly fused nuclei also exhibit divergent gene expression that is determined by the syncytial environment they fuse into. Moreover, accrual of additional nuclei through fusion is required for nuclei already resident in adult myofibers to mount a normal transcriptional response to a load-induced stimulus. We propose a model of mutual regulation in the control of skeletal muscle development and adaptations, where newly fused and pre-existing myonuclei influence each other to maintain optimal functional growth.

2023-08-23 | GSE241035 | GEO

Mouse myoblast fusion - Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190

Project description:The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes that they regulate remain poorly defined. Here we find that activity of p38α/β is important not only for early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treating C2 myoblasts with the pro-myogenic growth factor, IGF-I, we were able to overcome the early block in differentiation imposed by co-incubation with the p38 chemical inhibitor, SB202190. Yet, IGF-I could not overcome the later impairment of muscle cell fusion, as marked by the nearly complete absence of multinucleated myofibers. Removal of SB202190 from the medium of differentiating myoblasts showed that the fusion block was reversible, as multinucleated myofibers were detected several hours later, and reached ~90% of the culture within 30 hours. Analysis by quantitative mass spectroscopy of proteins that changed in abundance following removal of the inhibitor revealed a cohort of up-regulated muscle-enriched molecules that may be important for both myofibrillogenesis and fusion. We have thus developed a model system that allows separation of myoblast differentiation from muscle cell fusion, which should be useful in identifying specific steps regulated by p38 MAP kinase-mediated signaling in myogenesis.

2018-10-24 | PXD002413 | Pride

miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.

2012-04-30 | E-GEOD-36077 | biostudies-arrayexpress

Subcellular localization analysis of long non-non coding RNAs (lncRNAs) in skeletal muscle myofibers

Project description:In order to study the subcellular localization of lncRNAs in myofibers of skeletal muscle, single myofibers were isolated from Soleus, Extensor Digitorum Longus (EDL) and Tibialis Anterior (TA) of 9 mice. RNA was extracted from nuclei and cytoplasmic fractions of 5-10 isolated myofibers and than separately hybridized on microarrays. Preferential expression in nuclear or cytoplasmic compartment of each lncRNA was determined.

2019-01-07 | GSE112768 | GEO

miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

2012-05-01 | GSE36077 | GEO

Reorganization of chromatin architecture during prenatal development of porcine skeletal muscle

Project description:Myofibers (primary and secondary myofiber) are the basic structure of muscle and the determinant of muscle mass. To explore the skeletal muscle developmental processes from primary myofibers to secondary myofibers, we conducted an integrative 3D structure of genome and transcriptomic characterization of longissimus dorsi muscle (LDM) of pig from primary myofiber formation stage [embryonic day 35 (E35)] to secondary myofiber formation stage (E80). In the hierarchical genomic structure, we found that 11.43% of genome switched compartment A/B status, 14.53% of topologically associating domains (TADs) are changed intra- domain interactions (D-scores) and 3,166 genes with differential promoter-enhancer interactions (PEIs) and (or) enhancer activation from E35 to E80. The alterations of genome architecture were found to affect expression of genes that play significant roles in neuromuscular junction (NMJ) and embryonic morphogenesis in E35, such as NEFL, BRINP1, NTNG1, and MuSK and that function on skeletal muscle development or metabolism, typically MYL1, SLN, Sox6 and Mef2D.

2021-06-03 | GSE166346 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data