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Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [ATAC-Seq]

ABSTRACT: We performed a thorough study to analyze the epigenetic suppression of genes enabling programmed cell death as part of the muscle regeneration program. ATACseq analysis here serves as a method to compare the chromatin state and accessibilty of MuSCs in their quiescent state.

ORGANISM(S): Mus musculus

PROVIDER: GSE117092 | GEO | 2020/04/02

REPOSITORIES: GEO

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Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [RNA-seq 1]

Project description:We performed a thorough study to analyze the epigenetic suppression of genes enabling programmed cell death as part of the muscle regeneration program. RNAseq analysis here serves as a method to compare the differentially deregulated genes upon knockdown of Chd4 in MuSCs using Adenoviral CRE recombination.

2020-04-02 | GSE117008 | GEO

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [RNA-seq 3]

Project description:We performed a thorough study to analyze the epigenetic regulation of genes enabling programmed cell death as part of the chronic muscle regeneration.

2020-04-02 | GSE134132 | GEO

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [RNA-seq 2]

Project description:We performed a thorough study to analyze the epigenetic suppression of genes enabling programmed cell death as part of the muscle regeneration program.

2020-04-02 | GSE134131 | GEO

Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.

Project description:Somatic stem cells expand massively during tissue regeneration, which might require control of cell fitness, allowing elimination of non-competitive, potentially harmful cells. How or if such cells are removed to restore organ function is not fully understood. Here, we show that a substantial fraction of muscle stem cells (MuSCs) undergo necroptosis because of epigenetic rewiring during chronic skeletal muscle regeneration, which is required for efficient regeneration of dystrophic muscles. Inhibition of necroptosis strongly enhances suppression of MuSC expansion in a non-cell-autonomous manner. Prevention of necroptosis in MuSCs of healthy muscles is mediated by the chromatin remodeler CHD4, which directly represses the necroptotic effector Ripk3, while CHD4-dependent Ripk3 repression is dramatically attenuated in dystrophic muscles. Loss of Ripk3 repression by inactivation of Chd4 causes massive necroptosis of MuSCs, abolishing regeneration. Our study demonstrates how programmed cell death in MuSCs is tightly controlled to achieve optimal tissue regeneration.

| S-EPMC7242912 | biostudies-literature

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-02 | GSE134313 | GEO

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle

Project description:Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle

| PRJNA554685 | ENA

Muscle Stem Cell Response to Perturbations of the Neuromuscular Junction Are Attenuated With Aging

Project description:During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function, which is often associated with denervation and a loss of muscle stem cells (MuSCs). A relationship between MuSCs and innervation has not been established however. Herein, we administered neuromuscular trauma to a MuSC lineage tracing model and observed a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ). In aging and in a model of neuromuscular degeneration (Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ and partially restored MuSC ability to engraft into NMJ proximal positions. Using single cell RNA-sequencing of MuSCs, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury. These data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

2021-05-06 | GSE165978 | GEO

Chd4 controls Ripk3 dependent necroptosis during muscle regeneration

Project description:We performed a label-free LC-MS/MS study to analyse the role of Chd4 regulation in MuSC in suppressing genes enabling programmed cell death as part of the muscle regeneration program. Lox-cre recombination was used to create a deletion mutant of the CHD4 chromatin modifier (exons 12-21). A pseudo "infection" with GFP was used as control. Proteomics analysis here serves as a method to compare the differentially deregulated proteins upon knockdown of Chd4 in MuSCs using Adenoviral CRE recombination.

2020-04-02 | PXD010370 | Pride

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [ATAC-Seq]

Project description:Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscle [ATAC-Seq]

| PRJNA481035 | ENA

Paxbp1 is indispensable for cell cycle re-entry of adult muscle stem cells

Project description:Adult muscle stem cells (MuSCs) transit from a quiescent state to a highly proliferative state to support muscle repair. Paxbp1 deletion in MuSCs blocked their cell cycle re-entry and caused subsequent muscle regeneration failures. To understand the underlying molecular mechanisms, we compared the transcriptomes of control and Paxbp1 mutant MuSCs by RNA-seq. Our data confirmed a marked repression of cell cycle machineries in Paxbp1 mutant MuSCs. We also uncovered down-regulation of mutliple metabolic pathways in mutant MuSCs. In summary, our study highlights an essential role of Paxbp1 in MuSCs growth and cell cycle re-entry.

2021-03-23 | GSE141881 | GEO

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