Single-cell transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states associated with senescence

Walter, Lauren D.; Orton, Jessica L.; Fong, Ern Hwei Hannah; Maymi, Viviana I.; Rudd, Brian D.; Elisseeff, Jennifer H.; Cosgrove, Benjamin D.

doi:10.1101/2023.05.25.542370

Cited by 7 publications

(2 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2C). Seven clusters of cell types were identified based on differential gene expression, referring to previous studies on muscle scRNA-seq [30][31][32][33][34][35][36][37][38][39][40][41][42], namely myocytes (ACTN2, ACTN3, and MYO18B), fibroblast/fibro/adipogenic progenitors (FAPs) (PDGFRA, SMOC2, APOD, and GPX3), satellite cells (PAX7 and TAGLN3), endothelial cells (CDH5, PECAM1, and VWF), macrophage (CD163, PTPRC, and SRGN), pericytes (RGS5, KCNJ8, and ACTA2), and adipocytes (ADIPOQ, DGAT2, and PLIN1) (Fig. 2D).…”

Section: Snrna-seq Identified Distinct Cell Populations In Porcine Lo...mentioning

confidence: 99%

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle

Yi,

Li,

Zhu

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

Background Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs (DHM, IMF: 7.98% ± 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% ± 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics. Results A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05). Conclusions C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation.

show abstract

Section: Snrna-seq Identified Distinct Cell Populations In Porcine Lo...mentioning

confidence: 99%

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle

Yi,

Li,

Zhu

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

show abstract

“…The collected results led us to postulate that LAMs with high Pparg expression (Pparg HIGH ) take part in tissue regeneration. To demonstrate that we analyzed scRNAseq data of Notexin-treated skeletal muscle (GSE143437), a well-established regenerative model (Walter et al, 2023). We considered injured muscles at 0, 2, 5 and 7 days Notexin postinjection.…”

Section: Pparγ As a Potential Driver Of Regenerative Macrophagesmentioning

confidence: 99%

MACanalyzeR: scRNA-seq Analysis Tool Reveals PPARγHI Lipid-Associated Macrophages Facilitate Thermogenic Expansion in BAT

Ninni,

Zaccaria,

Verteramo

et al. 2024

Preprint

View full text Add to dashboard Cite

Macrophages in brown adipose tissue (BAT) play a complex role in regulating its activity. However, the role of macrophages in regulating BAT activation/deactivation has not yet been comprehensively characterized. To elucidate this, we developed MACanalyzeR, a scRNAseq-based tool specifically designed to explore the macrophage features at molecular and metabolic level. MACanalyzeR was applied in scRNA-seq datasets obtained from BAT with thermogenic loss (db/db mice) and activation (High Fat Diet, HFD). Our computational approach revealed that macrophages accumulating in BAT upon these conditions resemble lipid-associated macrophages (LAMs) with foaming-like features. BAT LAMs also show a significant enrichment of genes associated with mitochondria and lysosomes. Interestingly, LAMs identified in BAT from HFD mice positively correlate with thermogenic genes and exhibit an enrichment in PPARγ signaling pathway, with an activated mitochondrial metabolism. Cell dynamic strategy, revealed that LAM with high Pparg expression levels (PpargHIGH) progressively accumulate during skeletal muscle regeneration, suggesting a potential role for this LAM subcluster in maintaining tissue homeostasis. Our findings suggest PpargHIGH LAMs as a subclass of macrophages potentially contributing in preserving tissue homeostasis associated with high energy demand conditions such as thermogenic and regenerative stimuli.

show abstract

Muscle stem cell dysfunction in rhabdomyosarcoma and muscular dystrophy

Robertson,

Li,

Filippelli

et al. 2024

Current Topics in Developmental Biology

View full text Add to dashboard Cite

Single-cell transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states associated with senescence

Cited by 7 publications

References 64 publications

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle

MACanalyzeR: scRNA-seq Analysis Tool Reveals PPARγHI Lipid-Associated Macrophages Facilitate Thermogenic Expansion in BAT

Muscle stem cell dysfunction in rhabdomyosarcoma and muscular dystrophy

Contact Info

Product

Resources

About