High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations.

Adult tissue repair and regeneration require stem-progenitor cells that can self-renew and generate differentiated progeny. Skeletal muscle regenerative capacity relies on muscle satellite cells (MuSCs) and their interplay with different cell types within the niche. However, our understanding of skeletal muscle tissue cellular composition is limited. Here, using a combined approach of single-cell RNA sequencing and mass cytometry, we precisely mapped 10 different mononuclear cell types in adult mouse muscle. We also characterized gene signatures and determined key discriminating markers of each cell type. We identified two previously understudied cell populations in the interstitial compartment. One expresses the transcription factor scleraxis and generated tenocytes in vitro. The second expresses markers of smooth muscle and mesenchymal cells (SMMCs) and, while distinct from MuSCs, exhibited myogenic potential and promoted MuSC engraftment following transplantation. The blueprint presented here yields crucial insights into muscle-resident cell-type identities and can be exploited to study muscle diseases.

• Publication year

  2019

• Venue

  Molecules and Cells

• Publication date

  2019-05-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.molcel.2019.02.026PMID 30922843
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Transient and lineage-restricted requirement of Ebf3 for sternum ossification

  2020cited by this paper
• Tenogenic Contribution to Skeletal Muscle Regeneration: The Secretome of Scleraxis Overexpressing Mesenchymal Stem Cells Enhances Myogenic Differentiation In Vitro

  2020cited by this paper
• Temporal Dynamics and Heterogeneity of Cell Populations during Skeletal Muscle Regeneration

  2020cited by this paper
• Aging induces aberrant state transition kinetics in murine muscle stem cells

  2020cited by this paper
• H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles

  2019cited by this paper
• A molecular atlas of cell types and zonation in the brain vasculature

  2018cited by this paper
• Denervation-activated STAT3–IL-6 signalling in fibro-adipogenic progenitors promotes myofibres atrophy and fibrosis

  2018cited by this paper
• Mapping the Mouse Cell Atlas by Microwell-Seq.

  2018cited by this paper
• Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart.

  2018cited by this paper
• Integrating single-cell transcriptomic data across different conditions, technologies, and species

  2018cited by this paper
• Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris

  2018cited by this paper
• A Twist2-Dependent Progenitor Cell Contributes to Adult Skeletal Muscle

  2017cited by this paper
• High-resolution myogenic lineage mapping by single-cell mass cytometry

  2017cited by this paper
• Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages

  2017cited by this paper
• An NF-κB--EphrinA5-Dependent Communication between NG2(+) Interstitial Cells and Myoblasts Promotes Muscle Growth in Neonates.

  2016cited by this paper
• Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown

  2016cited by this paper
• Single-cell analysis reveals a nestin+ tendon stem/progenitor cell population with strong tenogenic potentiality

  2016cited by this paper
• Automated Mapping of Phenotype Space with Single-Cell Data

  2016cited by this paper
• Ballgown bridges the gap between transcriptome assembly and expression analysis

  2015cited by this paper
• Pervasive satellite cell contribution to uninjured adult muscle fibers

  2015cited by this paper
• HISAT: a fast spliced aligner with low memory requirements

  2015cited by this paper
• Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting

  2015cited by this paper
• StringTie enables improved reconstruction of a transcriptome from RNA-seq reads

  2015cited by this paper
• Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool

  2013cited by this paper
• Satellite cells and the muscle stem cell niche.

  2013cited by this paper
• Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice

  2013cited by this paper
• viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia

  2013cited by this paper
• The Rag2-Il2rb-Dmd- Mouse: a Novel Dystrophic and Immunodeficient Model to Assess Innovating Therapeutic Strategies for Muscular Dystrophies.

  2013cited by this paper
• Donor Satellite Cell Engraftment is Significantly Augmented When the Host Niche is Preserved and Endogenous Satellite Cells are Incapacitated

  2012cited by this paper
• Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells.

  2011cited by this paper
• Extracting a Cellular Hierarchy from High-dimensional Cytometry Data with SPADE

  2011cited by this paper
• Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration

  2011cited by this paper
• Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle

  2011cited by this paper
• An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration

  2011cited by this paper
• Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

  2011cited by this paper
• RNA-Seq analysis to capture the transcriptome landscape of a single cell

  2010cited by this paper
• Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis

  2010cited by this paper
• Multilevel Compression of Random Walks on Networks Reveals Hierarchical Organization in Large Integrated Systems

  2010cited by this paper
• Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle

  2010cited by this paper
• Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates

  2010cited by this paper
• Web‐Based Analysis and Publication of Flow Cytometry Experiments

  2010cited by this paper
• ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays.

  2009cited by this paper
• Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE.

  2009cited by this paper
• A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

  2009cited by this paper
• The Sequence Alignment/Map format and SAMtools

  2009cited by this paper
• Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry.

  2009cited by this paper
• Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates.

  2009cited by this paper
• Self-renewal and expansion of single transplanted muscle stem cells

  2008cited by this paper
• Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

  2007cited by this paper
• Generation of transgenic tendon reporters, ScxGFP and ScxAP, using regulatory elements of the scleraxis gene

  2007cited by this paper
• Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons

  2007cited by this paper
• Interleukin 15–dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation

  2006cited by this paper
• Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

  2005cited by this paper
• Mesoangioblasts--vascular progenitors for extravascular mesodermal tissues.

  2003cited by this paper
• Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.

  2001cited by this paper
• Relation between myofibers and connective tissue during muscle injury repair

  2000cited by this paper
• Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon

  1994cited by this paper

• Deciphering the cellular basis of heterosis in pigs through single-cell transcriptomics of growth axis-related tissues

  2026cites this paper
• Specific non-myogenic mesenchymal cells contribute to rotator cuff tear myosteatosis and fibrosis revealing novel therapeutic options

  2026cites this paper
• Single-Nucleus RNA Sequencing Reveals Cellular Heterogeneity and Trajectories of Lineage Differentiation during Chicken Skeletal Muscle Development.

  2026cites this paper
• Single-Cell Sequencing Reveals the Crosstalk Between MuSCs and FAPs in Ruminant Skeletal Muscle Development

  2026influential citation
• Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity

  2026cites this paper
• Generation of multitissue cell-cultivated meat via multidirectional differentiation of stable porcine epiblast stem cells.

  2026cites this paper
• Profiling the epigenomic landscape of late embryonic and adult mouse hind limb muscles.

  2026cites this paper
• Mouse skeletal muscle satellite cells co-opt the tenogenic gene Scleraxis to instruct regeneration

  2026cites this paper
• The contribution of skeletal muscle interstitial cells to myogenesis

  2026cites this paper
• Protocol to assess myogenic effects of 3T3-L1 and primary murine fibro-adipogenic progenitors on C2C12 myoblast differentiation

  2026cites this paper
• Rejuvenation-Responsive and Senolytic-Sensitive Muscle Stem Cells Unveiled by CD200 and CD63 in Geriatric Muscle

  2026cites this paper
• Age‐Associated Dysregulation of Postsynaptic Mitochondria Perturbs Reinnervation Kinetics

  2026cites this paper
• Isolation and purification of different high-purity cell populations from pig muscle tissue

  2025cites this paper
• The role of oxidative stress-mediated fibro-adipogenic progenitor senescence in skeletal muscle regeneration and repair

  2025cites this paper
• Single-cell transcriptome reveals three types of adipocytes associated with intramuscular fat content in pigs.

  2025cites this paper
• Temporal dynamics of the interstitial fluid proteome in human skeletal muscle following exhaustive exercise

  2025cites this paper
• Reducing Bias in Mass Cytometry Data through Corrections for Spillover and Nonspecific Binding.

  2025cites this paper
• Novel sACE2-Anti-CD16VHH Fusion Protein Surreptitiously Inhibits SARS-CoV-2 Variant Spike Proteins and Macrophage Cytokines, and Activates Natural Killer Cell Cytotoxicity

  2025cites this paper
• A Reassessment of Sarcopenia from a Redox Perspective as a Basis for Preventive and Therapeutic Interventions

  2025cites this paper
• Spatial and Multiomic profiling of muscle regeneration dynamics in Duchenne Muscular Dystrophy

  2025cites this paper
• Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle

  2025cites this paper
• The Molecular Mechanisms of Muscle–Adipose Crosstalk: Myokines, Adipokines, Lipokines and the Mediating Role of Exosomes

  2025cites this paper
• Histopathology and spatial transcriptomics jointly map myofiber-specific pathological programs in mTORC1-driven myopathy

  2025cites this paper
• Enhanced Media Optimize Bovine Myogenesis in 2D and 3D Models for Cultivated Meat Applications

  2025cites this paper
• Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis

  2025cites this paper
• Temporal single-cell sequencing analysis reveals that GPNMB-expressing macrophages potentiate muscle regeneration

  2025cites this paper
• Aging in the Skeletal Muscle Revealed by Molecular Immunohistochemical Imaging

  2025cites this paper
• Current cutting-edge omics techniques on musculoskeletal tissues and diseases

  2025cites this paper
• A primer on global molecular responses to exercise in skeletal muscle: Omics in focus

  2025cites this paper
• Single-cell RNA transcriptome uncovers distinct developmental trajectories in the embryonic skeletal muscle of Daheng broiler and Tibetan chicken

  2025cites this paper
• Physical Training Counteracts Mitochondrial Alterations in Myoblasts and Myotubes Derived From Muscle Satellite Cells of Old Mice: An In Vitro Ultrastructural Study.

  2025cites this paper
• Cellular Senescence in the Regenerative Niche Hampers Skeletal Muscle Repair

  2025cites this paper
• Crosstalk Between Skeletal Muscle and Proximal Connective Tissues in Lipid Dysregulation in Obesity and Type 2 Diabetes

  2025cites this paper
• Muscle stem cells in Duchenne muscular dystrophy exhibit molecular impairments and altered cell fate trajectories impacting regenerative capacity

  2025cites this paper
• Stage-specific requirement for METTL3-dependent m6A epitranscriptomic regulation during myogenesis

  2025cites this paper
• Hallmarks of stem cell aging.

  2025cites this paper
• Combined angiogenic and hypertrophic gene therapy enhances skeletal muscle growth.

  2025cites this paper
• mRNA-based in vivo induction of ETV2 to restore blood flow in a preclinical mouse hindlimb ischemia model

  2025cites this paper
• A Comprehensive View of Muscle Glucose Uptake: Regulation by Insulin, Contractile Activity and Exercise.

  2025cites this paper
• Estrogen rescues muscle regeneration impaired by DUX4 in a humanized xenograft mouse model

  2025cites this paper
• Molecular constraints of sarcopenia in the ageing muscle

  2025cites this paper
• FAP-CAR-T cells reduce dystrophic muscle fibrosis, improving adeno-associated virus gene transfer efficacy

  2025cites this paper
• Anti-fibrotic, muscle-promoting antibody-drug conjugates for the improvement and treatment of DMD

  2025cites this paper
• Optimizing 2D in vitro differentiation conditions for C2C12 murine myoblasts on gelatin hydrogel

  2025cites this paper
• Transcriptomic Analysis of Skeletal Muscle Systems Comparing Bovines, Humans, and Mice Using scRNA‐Seq

  2025cites this paper
• Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity

  2025cites this paper
• Cytokine expression and cytokine‐mediated cell–cell communication during skeletal muscle regeneration revealed by integrative analysis of single‐cell RNA sequencing data

  2024cites this paper
• MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis.

  2024cites this paper
• Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states

  2024cites this paper
• A novel ex vivo model of muscle contraction to measure muscle endocrine and paracrine signalling

  2024cites this paper
• Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets.

  2024cites this paper
• Beyond the bulk: overview and novel insights into the dynamics of muscle satellite cells during muscle regeneration

  2024cites this paper
• Uncovering the Embryonic Origins of Duchenne Muscular Dystrophy.

  2024cites this paper
• Single-cell sequencing to multi-omics: technologies and applications

  2024cites this paper
• Single-nucleus multiomics unravels the genetic mechanisms underlying musk secretion in Chinese forest musk deer (Moschus berezovskii).

  2024cites this paper
• Spatiotemporal transcriptomic mapping of regenerative inflammation in skeletal muscle reveals a dynamic multilayered tissue architecture

  2024cites this paper
• Profound cellular defects attribute to muscular pathogenesis in the rhesus monkey model of Duchenne muscular dystrophy.

  2024cites this paper
• Metabolic regulation in adult and aging skeletal muscle stem cells

  2024cites this paper
• A comprehensive single-cell RNA transcriptomic analysis identifies a unique SPP1+ macrophages subgroup in aging skeletal muscle

  2024cites this paper
• The important role of cellular mechanical microenvironment in engineering structured cultivated meat: Recent advances

  2024cites this paper
• The immunology of sickness metabolism

  2024cites this paper
• Effect of NR1D1 on the proliferation and differentiation of yak skeletal muscle satellite cells

  2024cites this paper
• Insights into the epitranscriptomic role of N6-methyladenosine on aging skeletal muscle.

  2024cites this paper
• GSK3 regulation Wnt/β-catenin signaling affects adipogenesis in bovine skeletal muscle fibro/adipogenic progenitors.

  2024cites this paper
• Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation

  2024cites this paper
• Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity

  2024cites this paper
• Mini-MEndR: a miniaturized 96-well predictive assay to evaluate muscle stem cell-mediated repair

  2024cites this paper
• Single-cell analysis reveals conserved regulons shaping muscle stem cell behavior during development and aging in mammals

  2024cites this paper
• Advancing skeletal health and disease research with single-cell RNA sequencing

  2024cites this paper
• Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells

  2024cites this paper
• Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support

  2024cites this paper
• Molecular aspects of the exercise response and training adaptation in skeletal muscle

  2024cites this paper
• Role of microenvironment on muscle stem cell function in health, adaptation, and disease.

  2024cites this paper
• Identifying the miRNA-gene networks contributes to exploring paravertebral muscle degeneration's underlying pathogenesis and therapy strategy

  2024cites this paper
• Muscle stem cells as immunomodulator during regeneration.

  2024cites this paper
• Single-nucleus transcriptomics and chromatin accessibility analysis of musk gland development in Chinese forest musk deer (Moschus berezovskii).

  2024cites this paper
• Muscle stem cell niche dynamics during muscle homeostasis and regeneration.

  2024cites this paper
• Effects of the immune system on muscle regeneration.

  2024cites this paper
• LncRNA 4930581F22Rik promotes myogenic differentiation by regulating the ERK/MAPK signaling pathway

  2024cites this paper
• Regulation of muscle hypertrophy through granulin: Relayed communication among mesenchymal progenitors, macrophages, and satellite cells.

  2024cites this paper
• DNA Methylation in the Adaptive Response to Exercise

  2024cites this paper
• Temporal Single-Cell Sequencing Analysis Reveals That GPNMB-Expressing Macrophages Potentiate Muscle Regeneration

  2024cites this paper
• Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments.

  2024cites this paper
• Functional specialisation and coordination of myonuclei

  2024cites this paper
• Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

  2024cites this paper
• mini-MEndR: A 96-well mixed species culture assay to co-evaluate human and mouse Pax7+ cell-mediated skeletal muscle repair

  2024cites this paper
• Human skeletal muscle aging atlas

  2024cites this paper
• Single-cell RNA sequencing unveils the activation of EGR1-ATF3 signaling in EGR1 + muscle stem cells during human paravertebral muscle degeneration

  2024cites this paper
• Characterizing the skeletal muscle immune microenvironment for sarcopenia using transcriptome analysis and histological validation

  2024cites this paper
• Integrated meta-omics reveals the regulatory landscape involved in lipid metabolism between pig breeds

  2024cites this paper
• Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration

  2024cites this paper
• Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging

  2024cites this paper
• Biology and physiology of tendon healing.

  2024cites this paper
• Macrophage-Myofibroblast Transition as a Potential Origin for Skeletal Muscle Fibrosis After Injury via Complement System Activation

  2024cites this paper
• The reciprocity of skeletal muscle and bone: an evolving view from mechanical coupling, secretory crosstalk to stem cell exchange

  2024cites this paper
• Characterization of the Immune Microenvironment and Identification of Biomarkers in Chronic Rhinosinusitis with Nasal Polyps Using Single-Cell RNA Sequencing and Transcriptome Analysis

  2024cites this paper
• Single-cell transcriptional profiling of porcine muscle satellite cells and myoblasts during myogenesis

  2024cites this paper
• Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

  2024cites this paper
• Generating detailed intercellular communication patterns in psoriasis at the single-cell level using social networking, pattern recognition, and manifold learning methods to optimize treatment strategies

  2024cites this paper
• Lipidomics and single-cell RNA sequencing reveal lipid and cell dynamics of porcine glycerol-injured skeletal muscle regeneration model.

  2024cites this paper