Satellite cell depletion results in a cryptic subpopulation of myonuclei in response to exercise
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ABSTRACT:
PROVIDER: PRJNA681403 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13163481.fastq.gz | Fastqsanger.gz | |||
| SRR13163482.fastq.gz | Fastqsanger.gz | |||
| SRR13163483.fastq.gz | Fastqsanger.gz | |||
| SRR13163484.fastq.gz | Fastqsanger.gz | |||
| SRR13163485.fastq.gz | Fastqsanger.gz |
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Project description:Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle from sedentary mice that is altered by 4 weeks of exercise training. Furthermore, in response to exercise, snRNA-seq reveals that resident muscle stem cells, satellite cells, were activated, but demonstrated limited lineage progression while contributing to muscle adaption. In the absence of satellite cells, trajectory analysis predicts the emergence of cryptic myonuclei that appear to lose their canonical identity. These data illustrate how myonuclear adaptation to exercise may be disrupted under conditions satellite cell compromise.
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Project description:Purpose:To identify genes and the molecular pathways involved in the regulation of muscle satellite cells (SCs) in mice exposure to running exercise, we performed RNA-Sequence of SCs in untrained (Con) and trained mice (Exe). Methods: mRNA profiles of SCs in untrained (Con) and trained mice (Exe) (running exercise, 4 days/week, 30 min/day at 12 m/min) were generated by deep sequencing, in quadruplicate, using Illumina HiSeq 2000. Results:Using an optimized data analysis workflow, we mapped about 9 million sequence reads per sample to the mouse genome (build mm10) and identified 9031 transcripts in SCs (the control and exercise group) with BWA workflow. Conclusions: Our results represent the first detailed analysis of SCs transcriptomes in mice exposure to running exercise and found that exercise regulated multiple mRNA pathways in SCs.
2020-06-08 | GSE128651 | GEO
Project description:(Abstract of publication submitted currently) To clarify molecular regulation of satellite cells, we performed genome-wide gene expression analysis of quiescent satellite cells isolated from mouse skeletal muscle by flow cytometry. We identified 53 novel quiescent satellite cell-specific genes whose expressions are sharply down-regulated upon activation. The gene list contains a number of cell surface molecules, transcriptional factors, and cytokines and other signal transduction molecules. We further confirmed that Odz4 and calcitonin receptor proteins were expressed by quiescent but not by activated satellite cells in vivo. Importantly, we found that Pax7+/calcitonin receptor+ satellite cells reappear in close association with regenerating myofibers 7 days after muscle damage, often outside the basal lamina. Moreover, an agonist of calcitonin receptor suppressed the activation of quiescent satellite cells on myofibers in in vitro culture, suggesting that calcitonin receptor signaling plays an important role in renewal and maintenance of satellite cells. Our results show the gene expression profile of quiescent satellite cells for the first time and reveal the temporal and spatial reappearance of a satellite cell pool. Experiment Overall Design: Satellite cells and non-satellite cells were examined. Totally three types of cells (groups), the satellite cells in quiescent and activated states and the non-satellite cells, were compared. Each has 4 replicates.
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Project description:The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis. The data set contains one microarray of pooled quiescent skeletal muscle satellite cells
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Project description:Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neuronal stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.
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Project description:(Abstract of publication submitted currently) To clarify molecular regulation of satellite cells, we performed genome-wide gene expression analysis of quiescent satellite cells isolated from mouse skeletal muscle by flow cytometry. We identified 53 novel quiescent satellite cell-specific genes whose expressions are sharply down-regulated upon activation. The gene list contains a number of cell surface molecules, transcriptional factors, and cytokines and other signal transduction molecules. We further confirmed that Odz4 and calcitonin receptor proteins were expressed by quiescent but not by activated satellite cells in vivo. Importantly, we found that Pax7+/calcitonin receptor+ satellite cells reappear in close association with regenerating myofibers 7 days after muscle damage, often outside the basal lamina. Moreover, an agonist of calcitonin receptor suppressed the activation of quiescent satellite cells on myofibers in in vitro culture, suggesting that calcitonin receptor signaling plays an important role in renewal and maintenance of satellite cells. Our results show the gene expression profile of quiescent satellite cells for the first time and reveal the temporal and spatial reappearance of a satellite cell pool. Keywords: cell type comparison
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