Abstract 13681: Single-cell Gene Profiling Revealed Heterogeneity of Human Skeletal Muscle Derived Stem Cells and Their Paracrine Factors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hiroko Iseoka ◽  
Shigeru Miyagawa ◽  
Kosuke Torigata ◽  
Yoshiki Sawa
Keyword(s):  
Skeletal Muscle ◽  
Single Cell ◽  
Cell Population ◽  
Angiogenic Factors ◽  
Gene Profiling ◽  
Therapeutic Effects ◽  
Proliferating Cells ◽  
Paracrine Factors ◽  
Differentiated Cells ◽  
Cell Gene

Background: Transplantation of sheet-shaped autologous skeletal muscle-derived cells (SMDCs) has been shown to produce therapeutic effects via paracrine factors in ischemic cardiomyopathy. SMDCs are heterogeneous cell population consist of myoblasts and non-myogenic cells, and their detailed characteristic and paracrine factors has not been fully analyzed. We herein applied single-cell RNA sequencing (scRNA-seq) to profile the population and paracrine factors of SMDCs. Methods and Results: Primary SMDCs of human origin were subjected to scRNA-seq and divided into 5 populations, expressing myogenic markers differently. These included four myogenic populations with higher expression of MYF5 (myoblasts), myogenin (early differentiated cells), mitosis-related gene (proliferating cells), and MYL3 (moderately differentiated cells) and non-myogenic population with lower expression of myogenic genes. On the other hand, PAX7 , quiescent satellite cell marker, and MYH4 , terminally differentiated marker, were not expressed in any populations. Furthermore, regarding the expression of key angiogenic factors, VEGF and HGF were highly expressed in the non-myogenic population and HMGB1 was expressed in both populations. Moreover, analysis of the gene expression of angiogenic factors differentially expressed in each population indicated that myoblast population highly expressed PDGFA and CCN (Cellular communication network factor) 1 , and early differentiated population highly expressed CCN2 . Although these factors were expressed in other populations, their expression tended to be lower in the moderately differentiated cell population. Conclusion: Analysis of SMDCs using scRNA-seq revealed that they are heterogeneous cells consisting of multiple myogenic populations with different degrees of differentiation and cytokine production, suggesting that single-cell gene profiling may be useful for the evaluation on characters of effector cells.

scholarly journals Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1

2020 ◽  
Vol 21 (17) ◽  
pp. 6269
Author(s):  
Alee Choi ◽  
Sang Eon Park ◽  
Jang Bin Jeong ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Wharton's Jelly ◽  
Muscle Fibrosis ◽  
Skeletal Muscle Fibrosis

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

scholarly journals Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis

Development ◽  
2008 ◽  
Vol 135 (18) ◽  
pp. 3113-3124 ◽  
Author(s):  
A. Kawaguchi ◽  
T. Ikawa ◽  
T. Kasukawa ◽  
H. R. Ueda ◽  
K. Kurimoto ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Profiling ◽  
Cell Gene

scholarly journals Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted murine heart

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Julia Hesse ◽  
Christoph Owenier ◽  
Tobias Lautwein ◽  
Ria Zalfen ◽  
Jonas F Weber ◽  
...  
Keyword(s):  
Single Cell ◽  
Stromal Cells ◽  
Wilms Tumor ◽  
Hypoxia Inducible Factor ◽  
Lineage Tracing ◽  
Proliferating Cells ◽  
Paracrine Factors ◽  
Epicardial Cells ◽  
Cardiac Specification ◽  
Rna In Situ Hybridization

In the adult heart, the epicardium becomes activated after injury, contributing to cardiac healing by secretion of paracrine factors. Here, we analyzed by single-cell RNA sequencing combined with RNA in situ hybridization and lineage tracing of Wilms tumor protein 1-positive (WT1+) cells, the cellular composition, location, and hierarchy of epicardial stromal cells (EpiSC) in comparison to activated myocardial fibroblasts/stromal cells in infarcted mouse hearts. We identified 11 transcriptionally distinct EpiSC populations, which can be classified into three groups, each containing a cluster of proliferating cells. Two groups expressed cardiac specification markers and sarcomeric proteins suggestive of cardiomyogenic potential. Transcripts of hypoxia-inducible factor (HIF)-1α and HIF-responsive genes were enriched in EpiSC consistent with an epicardial hypoxic niche. Expression of paracrine factors was not limited to WT1+ cells but was a general feature of activated cardiac stromal cells. Our findings provide the cellular framework by which myocardial ischemia may trigger in EpiSC the formation of cardioprotective/regenerative responses.

scholarly journals Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted heart

2021 ◽  
Author(s):  
Julia Hesse ◽  
Christoph Owenier ◽  
Tobias Lautwein ◽  
Ria Zalfen ◽  
Jonas F. Weber ◽  
...  
Keyword(s):  
Single Cell ◽  
Stromal Cells ◽  
Lineage Tracing ◽  
Sarcomeric Proteins ◽  
Proliferating Cells ◽  
Paracrine Factors ◽  
Epicardial Cells ◽  
Cardiac Specification ◽  
Rna In Situ Hybridization

AbstractIn the adult heart, the epicardium becomes activated after injury, contributing to cardiac healing by secretion of paracrine factors. Here we analyzed by single-cell RNA sequencing combined with RNA in situ hybridization and lineage tracing of WT1+ cells the cellular composition, location, and hierarchy of epicardial stromal cells (EpiSC) in comparison to activated myocardial fibroblasts/stromal cells in infarcted mouse hearts. We identified 11 transcriptionally distinct EpiSC populations, that can be classified in three groups each containing a cluster of proliferating cells. Two groups expressed cardiac specification makers and sarcomeric proteins suggestive of cardiomyogenic potential. Transcripts of HIF-1α and HIF-responsive genes were enriched in EpiSC consistent with an epicardial hypoxic niche. Expression of paracrine factors was not limited to WT1+ cells but was a general feature of activated cardiac stromal cells. Our findings provide the cellular framework by which myocardial ischemia may trigger in EpiSC the formation of cardioprotective/regenerative responses.

Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors

2020 ◽  
Vol 77 (24) ◽  
pp. 5299-5320
Author(s):  
Jiacheng Deng ◽  
Zhichao Ni ◽  
Wenduo Gu ◽  
Qishan Chen ◽  
Witold Norbert Nowak ◽  
...  
Keyword(s):  
Single Cell ◽  
Lineage Tracing ◽  
Gene Profiling ◽  
Endothelial Repair ◽  
Cell Gene

Single-cell gene profiling of planarian stem cells using fluorescent activated cell sorting and its “index sorting” function for stem cell research

2010 ◽  
Vol 52 (1) ◽  
pp. 131-144 ◽  
Author(s):  
Tetsutaro Hayashi ◽  
Norito Shibata ◽  
Ryo Okumura ◽  
Tomomi Kudome ◽  
Osamu Nishimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Stem Cell Research ◽  
Cell Sorting ◽  
Gene Profiling ◽  
Cell Gene ◽  
Index Sorting

scholarly journals Single Cell Gene Profiling Revealed Heterogeneity of Paracrine Effects of Bone Marrow Cells in Mouse Infarcted Hearts

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68270 ◽  
Author(s):  
Yanhua Li ◽  
Xinhong Guo ◽  
Qiao Xue ◽  
Mei Zhu ◽  
Lei Gao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Cell ◽  
Bone Marrow Cells ◽  
Gene Profiling ◽  
Paracrine Effects ◽  
Cell Gene ◽  
Marrow Cells

scholarly journals Slingshot: Cell lineage and pseudotime inference for single-cell transcriptomics

2017 ◽  
Author(s):  
Kelly Street ◽  
Davide Risso ◽  
Russell B. Fletcher ◽  
Diya Das ◽  
John Ngai ◽  
...  
Keyword(s):  
Single Cell ◽  
Branching Processes ◽  
Cell Lineage ◽  
Flexible Tool ◽  
Cell Lineages ◽  
Differentiated Cells ◽  
Multipotent Progenitors ◽  
Cell Gene Expression ◽  
Novel Method ◽  
Cell Gene

AbstractSingle-cell transcriptomics allows researchers to investigate complex communities of heterogeneous cells. These methods can be applied to stem cells and their descendants in order to chart the progression from multipotent progenitors to fully differentiated cells. While a number of statistical and computational methods have been proposed for analyzing cell lineages, the problem of accurately characterizing multiple branching lineages remains difficult to solve. Here, we introduce a novel method, Slingshot, for inferring multiple developmental lineages from single-cell gene expression data. Slingshot is a uniquely robust and flexible tool for inferring developmental lineages and ordering cells to reflect continuous, branching processes.

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