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

Giordani, Lorenzo; He, Gary J.; Négroni, Elisa; Sakai, Hiroshi; Law, Justin; Siu, M. Mona; Wan, Raymond; Corneau, Aurélien; Tajbakhsh, Shahragim; Cheung, Tom H.; Grand, Fabien Le

doi:10.1016/j.molcel.2019.02.026

Cited by 311 publications

(209 citation statements)

References 56 publications

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“…It should be kept in mind that cell types other than multinucleated fibers reside in skeletal muscles, including satellite cells, immune cells, fibro-adipogenic precursor cells, endothelial cells, and glial cells. These distinct cell type populations express different molecular signatures, as determined recently using a combination of single-cell mass cytometry and single-cell transcriptomics [102]. The changes we report here, which were derived from the analysis of whole muscle isolates, may therefore be influenced by changes in relative proportions of individual cell type populations and their specific response to food deprivation.…”

Section: Discussionmentioning

confidence: 55%

Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

Ibrahim

Wasselin

Challet

et al. 2020

IJMS

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Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.

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Section: Discussionmentioning

confidence: 55%

Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

Ibrahim

Wasselin

Challet

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…We identified several clusters of myonuclei belonging to multinucleated muscle fibers, characterized by expression of numerous canonical myonuclear transcripts such as Tnnt3, Mybpc1, and Mybpc2 (Extended Data Fig. 2), and constituting a population essentially excluded by conventional single-cell analyses of skeletal muscle 12,13 .…”

Section: Mainmentioning

confidence: 99%

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

Petrany

Swoboda

Sun

et al. 2020

Preprint

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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.

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“…All the skeletal muscle in the trunk, including pectoral muscles, are derived from somites. However, skeletal muscle tissues are complex because different types of MCT cells intercalate into muscle fibers, and these MCT cell lineages are heterogeneous (Giordani et al, 2019). Recent studies on skeletal myogenesis have focused on MCT cells, which play crucial roles in muscle development and maintenance (Sefton and Kardon, 2019).…”

Section: Introductionmentioning

confidence: 99%

Transient and lineage-restricted requirement of Ebf3 for sternum ossification

et al. 2020

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Osteoblasts arise from bone-surrounding connective tissue containing tenocytes and fibroblasts. Lineages of these cell populations and mechanisms of their differentiation are not well understood. Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. Knockout of Ebf3 in mice had no effect on chondrogenesis but led to sternum ossification defects as a result of defective generation of Runx2 + pre-osteoblasts. Conditional and temporal Ebf3 knockout mice revealed requirements of Ebf3 in the lateral plate mesenchyme cells (LPMs), especially in tendon/muscle connective tissue cells, and a stage-specific Ebf3 requirement at embryonic day 9.5-10.5. Upregulated expression of connective tissue markers, such as Egr1/2 and Osr1, increased number of Islet1 + mesenchyme cells, and downregulation of gene expression of the Runx2 regulator Shox2 in Ebf3-deleted thoracic LPMs suggest crucial roles of Ebf3 in the onset of lateral plate mesoderm differentiation towards osteoblasts forming sternum tissues.

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

Abstract: Highlights d Combination of single-cell RNA sequencing and mass cytometry d Construction of a cell atlas of adult skeletal muscle d Skeletal muscle is composed of 10 mononucleated cell types and myofibers d Skeletal muscle contains interstitial tenocytes and smooth muscle-mesenchymal cells

Cited by 311 publications

References 56 publications

Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

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

Transient and lineage-restricted requirement of Ebf3 for sternum ossification

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