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

Cell Reports ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 3583-3595.e5 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Emily J. Laurilliard ◽  
Charles L. Heinke ◽  
Hiranmayi Ravichandran ◽  
Paula Fraczek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Single Cell ◽  
Muscle Regeneration ◽  
Single Cell Analysis ◽  
Skeletal Muscle Regeneration ◽  
Cell Analysis ◽  
Muscle Stem Cell ◽  
Communication Signals ◽  
Stem Cell Hierarchy

scholarly journals Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration

2019 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Paula Fraczek ◽  
Sharon Soueid-Baumgarten ◽  
Hiranmayi Ravichandran ◽  
Iwijn De Vlaminck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Single Cell ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Myogenic Cell ◽  
Skeletal Muscle Regeneration ◽  
Cell Populations ◽  
Communication Signals

AbstractMuscle stem cells (MuSCs) are an essential adult stem cell population with the capacity to self-renew and regenerate muscle tissue. Functionally heterogeneous subpopulations of MuSCs have been identified based on their expression of myogenic regulatory factors and surface markers. However, a unified organization of muscle stem and progenitor cells and their subpopulations remains unresolved. Here, we performed temporal analysis of skeletal muscle regeneration using single-cell RNA-sequencing (scRNA-seq) of myotoxin-injured adult mouse hindlimb muscles. We generated over 34,000 single-cell transcriptomes spanning four muscle regeneration time-points and identified 15 distinct cell types, including a heterogeneous population of MuSCs and progenitor cells. Our analysis provides a hierarchical map of myogenic cell populations and identifies stage-specific regulatory programs that govern their contributions to muscle regeneration. In this transcriptomic atlas, we observed cell type-specific regenerative dynamics, exemplified by waves of transient amplification and diversification of multiple immune cell types and, subsequently, myogenic cells. Unbiased trajectory inference organized the myogenic cell populations within the atlas into a continuum, consisting of a hierarchy of quiescent MuSCs, cycling progenitors, committed myoblasts, and terminally differentiated myocytes. This myogenic trajectory matched prior understanding and also revealed that MuSC stages are defined by synchronous changes in regulatory factors, cell cycle-associated, and surface receptor gene expression. Lastly, we analyzed the transcriptomic atlas to identify over 100 candidate heterotypic communication signals between myogenic and non-myogenic cell populations, including many involving the fibroblast growth factor (FGF), Notch, and Syndecan receptor families and their associated ligands. Syndecan receptors were implicated in a large fraction of these cell communication interactions and were observed to exhibit transcriptional heterogeneity within the myogenic continuum. Using multiparameter mass cytometry (CyTOF), we confirmed that cycling MuSCs exhibit diversified Syndecan-1/2 expression, which suggests that dynamic alterations in Syndecan signaling interactions may coordinate stage-specific myogenic cell fate regulation. This scRNA-seq reference atlas provides a resolved hierarchical organization of myogenic subpopulations as a resource to investigate cell-cell interactions that regulate myogenic stem and progenitor cell fates in muscle regeneration.

scholarly journals Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 744
Author(s):  
Matthew Borok ◽  
Nathalie Didier ◽  
Francesca Gattazzo ◽  
Teoman Ozturk ◽  
Aurelien Corneau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Skeletal Muscle Regeneration ◽  
Muscle Repair ◽  
Muscle Stem Cell ◽  
Muscle Stem Cells ◽  
Cell Lineages

Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.

scholarly journals Single-Cell Analysis of Proxy Reporter Allele-Marked Epithelial Cells Establishes Intestinal Stem Cell Hierarchy

2014 ◽  
Vol 3 (5) ◽  
pp. 876-891 ◽  
Author(s):  
Ning Li ◽  
Maryam Yousefi ◽  
Angela Nakauka-Ddamba ◽  
Rajan Jain ◽  
John Tobias ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Intestinal Stem Cell ◽  
Cell Analysis ◽  
Stem Cell Hierarchy

scholarly journals Satellite Cells and the Muscle Stem Cell Niche

2013 ◽  
Vol 93 (1) ◽  
pp. 23-67 ◽  
Author(s):  
Hang Yin ◽  
Feodor Price ◽  
Michael A. Rudnicki
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Stem Cell Niche ◽  
Skeletal Muscle Regeneration ◽  
Stem Cell Population ◽  
Muscle Stem Cell ◽  
Adult Skeletal Muscle ◽  
Cell Niche

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.

scholarly journals A cellular atlas of skeletal muscle regeneration and aging

2019 ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Elston ◽  
Rebecca O’Rourke ◽  
Kenneth Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Muscle Function ◽  
Immune Cell ◽  
Complex Structure ◽  
Skeletal Muscle Regeneration ◽  
Nerve Tissue ◽  
Post Injury ◽  
Muscle Stem Cell

SummaryAn individual skeletal muscle is a complex structure, composed of large contractile myofibers, connective tissue, nerve tissue, immune cells, stem cells and the vasculature. Each of these components contribute to skeletal muscle function, maintenance, regeneration, and if perturbed can potentially contribute to or cause disease that reduces muscle function. To investigate the cellular inventory of skeletal muscle we carried out single cell RNA sequencing on cells isolated from adult uninjured muscle, adult post injury muscle, and from aged uninjured muscle. Our muscle atlas provides the cellular landscape and partial transcriptome of pre-injury, post injury, and aged muscle, identifying dramatic changes in the muscle stem cell, fibroblast and immune cell populations during regeneration. Our data highlight dynamic changes occurring during muscle regeneration, identify potential extrinsic mechanisms that control muscle stem cell behavior, and underscore the inflamed state of aged uninjured muscle.

scholarly journals Colorectal Cancer Stem Cell States Uncovered by Simultaneous Single‐Cell Analysis of Transcriptome and Telomeres

2021 ◽  
Vol 8 (8) ◽  
pp. 2004320
Author(s):  
Hua Wang ◽  
Peng Gong ◽  
Tong Chen ◽  
Shan Gao ◽  
Zhenfeng Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Analysis

Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration

FEBS Letters ◽  
2015 ◽  
Vol 589 (11) ◽  
pp. 1257-1265 ◽  
Author(s):  
Yoshihiro Nakamura ◽  
Shigeru Miyaki ◽  
Hiroyuki Ishitobi ◽  
Sho Matsuyama ◽  
Tomoyuki Nakasa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration

scholarly journals Single-cell analysis of diversity in human stem cell-derived neurons

2017 ◽  
Vol 371 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Lise J. Harbom ◽  
Nadine Michel ◽  
Michael J. McConnell
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Human Stem Cell
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