Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration

Micheli, Andrea De; Laurilliard, Emily J.; Heinke, Charles L.; Ravichandran, Hiranmayi; Fraczek, Paula; Soueid-Baumgarten, Sharon; Vlaminck, Iwijn De; Elemento, Olivier; Cosgrove, Benjamin D.

doi:10.1016/j.celrep.2020.02.067

Cited by 258 publications

(247 citation statements)

References 61 publications

Supporting

Mentioning

210

Contrasting

Unclassified

Order By: Relevance

“…S2). Pericytes are likewise unannotated in multiple single cell genomics studies of the limb muscle [21,29,20,63]. We believe this is the first identification of this cell type in the muscle mononuclear population by single cell genomics, in agreement with histological literature noting its presence and importance [10,11].…”

Section: Single Cell Rna-sequencing Of Muscle Mononuclear Cells Identsupporting

confidence: 81%

Differentiation reveals the plasticity of age-related change in murine muscle progenitors

Kimmel

Hendrickson

Kelley

2020

Preprint

View full text Add to dashboard Cite

Skeletal muscle experiences a decline in lean mass and regenerative potential with age, in part due to intrinsic changes in progenitor cells. However, it remains unclear if age-related changes in progenitors persist across a differentiation trajectory or if new age-related changes manifest in differentiated cells. To investigate this possibility, we performed single cell RNA-seq on muscle mononuclear cells from young and aged mice and profiled muscle stem cells (MuSCs) and fibro/adipose progenitors (FAPs) after differentiation. Differentiation increased the magnitude of age-related change in MuSCs and FAPs, but also masked a subset of age-related changes present in progenitors. Using a dynamical systems approach and RNA velocity, we found that aged MuSCs follow the same differentiation trajectory as young cells, but stall in differentiation near a commitment decision. Our results suggest that age-related changes are plastic across differentiation trajectories and that fate commitment decisions are delayed in aged myogenic cells.

show abstract

Section: Single Cell Rna-sequencing Of Muscle Mononuclear Cells Identsupporting

confidence: 81%

Differentiation reveals the plasticity of age-related change in murine muscle progenitors

Kimmel

Hendrickson

Kelley

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The defined cellular populations during skeletal muscle regeneration are consistent with those from published myogenic single cell sequencing datasets, which suggests that acutely injured muscle undergoes similar mechanisms of cellular regeneration irrespective of the inciting injury (Barruet et al, 2020;De Micheli et al, 2020b;Dell'Orso et al, 2019b).…”

Section: Myogenic Cell Fate Transitions Revealed By Single Cell Rna Ssupporting

confidence: 75%

“…Single cell analyses of muscle regeneration demonstrate the rich cellular complexity governing myogenesis and make two key observations (De Micheli et al, 2020a;Dell'Orso et al, 2019a;Giordani et al, 2019). First, in response to damage, MuSCs exit quiescence and progress through a hierarchical, dynamic myogenic program as activated MuSCs either commit to terminal differentiation or self-renew and re-acquire a quiescent state.…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins Direct Myogenic Cell Fate Decisions

Wheeler

Whitney

Vogler

et al. 2021

Preprint

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) are essential for skeletal muscle regeneration and RBP dysfunction causes muscle degeneration and neuromuscular disease. How ubiquitously expressed RBPs orchestrate complex tissue regeneration and direct cell fate decisions in skeletal muscle remains poorly understood. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including numerous neuromuscular disease-associated RBPs, is temporally regulated in skeletal muscle stem cells and correlates to stages of myogenic differentiation. By combining machine learning with RBP engagement scoring, we discover that the neuromuscular disease associated RBP Hnrnpa2b1 is a differentiation-specifying regulator of myogenesis controlling myogenic cell fate transitions during terminal differentiation. The timing of RBP expression specifies cell fate transitions by providing a layer of post-transcriptional regulation needed to coordinate stem cell fate decisions during complex tissue regeneration.

show abstract

“…MuSC, muscle satellite cell; mRNA, messenger RNA immediately separated after the sciatic nerve damage was designated as group N. We performed RNA sequencing (RNA-seq) to assess the presence and quantity of the RNA content using three biological replicates at each time point (Table S1). A study analyzed the main group of cells that constituted the skeletal muscle as well as the specific markers of these cells, which were the endothelial cell marker (Cdh5), muscle satellite cells (MuSCs) makers (Pax7, Myod1, Myog, Myf5), mature skeletal muscle cells makers (Des, Tnnt3, Tnni2, Tnnc2, Acta1;De Micheli et al, 2020). Denervation has been reported to induce Myog expression in myofibers; therefore, in the present study, we only used the other three genes as MuSCs markers (Hitachi et al, 2019;Moresi et al, 2010).…”

Section: An Atrophy Phenotype Emerged Between 36 H and 3 Days Aftermentioning

confidence: 99%

Alternative splicing transitions associate with emerging atrophy phenotype during denervation‐induced skeletal muscle atrophy

Qiu

Chang

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Alternative splicing (AS) presents a key posttranscriptional regulatory mechanism associated with numerous physiological processes. However, little is known about its role in skeletal muscle atrophy. In this study, we used a rat model of denervated skeletal muscle atrophy and performed RNA-sequencing to analyze transcriptome profiling of tibialis anterior muscle at multiple time points following denervation. We found that AS is a novel mechanism involving muscle atrophy, which is independent changes at the transcript level. Bioinformatics analysis further revealed that AS transitions are associated with the appearance of the atrophic phenotype. Moreover, we found that the inclusion of multiple highly conserved exons of Obscn markedly increased at 3 days after denervation. In addition, we confirmed that this newly transcript inhibited C2C12 cell proliferation and exacerbated myotube atrophy. Finally, our study revealed that a large number of RNA-binding proteins were upregulated when the atrophy phenotype appeared. Our data emphasize the importance of AS in this process.

show abstract

Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration

Cited by 258 publications

References 61 publications

Differentiation reveals the plasticity of age-related change in murine muscle progenitors

Differentiation reveals the plasticity of age-related change in murine muscle progenitors

RNA-Binding Proteins Direct Myogenic Cell Fate Decisions

Alternative splicing transitions associate with emerging atrophy phenotype during denervation‐induced skeletal muscle atrophy

Contact Info

Product

Resources

About