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Comparative transcriptomic study of skeletal muscles response to muscular dystrophy with myositis

ABSTRACT: Comparative transcriptomic study of skeletal muscles response to muscular dystrophy with myositis

PROVIDER: PRJNA664747 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12682580_1.fastq.gz	Fastqsanger.gz
	SRR12682580_2.fastq.gz	Fastqsanger.gz
	SRR12682581_1.fastq.gz	Fastqsanger.gz
	SRR12682581_2.fastq.gz	Fastqsanger.gz
	SRR12682582_1.fastq.gz	Fastqsanger.gz

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Comparative transcriptomic study of skeletal muscles response to muscular dystrophy with myositis

Project description:Muscular dystrophy with myositis (mdm) is a severe degenerative muscle disease arising from a spontaneous mutaton at the N2A-PEVK junction of titin protein. The affected mice show a complex disease phenotype, and more organism-wide spread response compared to other myopathies. The project objectives forcus on undertanding the response pattetern of different skelelal muscles to mdm.

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Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice

Project description:Titinopathies are inherited muscular diseases triggered by genetic mutations in the titin gene. Muscular dystrophy with myositis (mdm) is one such disease caused by a deletion in the N2A-PEVK region of titin, one of the most active binding sites in titin, and mice with this deletion develop progressive muscle degeneration. The range of phenotypic differences observed in mdm mice extends well beyond impacts on titin, making it clear that deletion of this region initiates a cascade of additional transcriptomic changes. Previous research has focused on correlating phenotypic differences with muscle function in mdm mice. These studies have provided understanding of the downstream physiological effects resulting from the deletion but only provide insights on processes that can be physiologically observed and measured. We used differential gene expression (DGE) to compare the transcriptomes of extensor digitorum longus (EDL), psoas and soleus muscles from wild-type and mdm mice to develop a deeper understand of these tissue-specific responses.

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Project description:Muscular dystrophy is a group of diseases that cause progressive weakness and degeneration of the skeletal muscles that control movement. Lacking the caveolae component polymerase I transcription release factor (PTRF) causes a secondary deficiency of caveolins resulting in muscular dystrophy. To investigate the effect of PTRF deletion on skeletal muscle, we created gene-edited mice with PTRF knockout (KO). We then performed RNA-seq of soleus and quadriceps muscles from soleus and quadriceps muscles of 3 months old WT (n=3) and PTRF KO mice (n=3) and analyzed the data for gene expression profiling. 12933 genes were detected across all 12 libraries. The hierarchy clustering of co-expressed genes revealed a clear split between PTRF KO and WT mice for both skeletal muscles. Differential expression analysis identified 1293 and 705 differentially expressed genes (DEGs) in the soleus and quadriceps, respectively. 971 and 534 DEGs were up-regulated, and 322 and 171 DEGs were down-regulated in the soleus and quadriceps of PTRF KO mice, respectively.

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Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice

Project description:Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice

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Decoding the transcriptome of muscular dystrophy using single-nucleus RNA sequencing

Project description:Muscular dystrophy is a group of diseases that cause progressive weakness and degeneration of the skeletal muscles that control movement. Lacking polymerase I transcription release factor (PTRF, also known as Cavin1), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. Because skeletal muscle is a heterogeneous tissue composed of different metabolic muscle fiber (myofibers) and mononuclear cells, the transcriptome responses of these myofibers and mononuclear cell to muscular dystrophy caused by PTRF deletion has not been explored. Here, we create muscular dystrophy mice caused by the deletion of PTRF gene and apply single-nucleus RNA sequencing (snRNA-seq) to unveil transcriptional changes in the skeletal muscle of mice with muscular dystrophy at single-nucleus resolution.

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Project description:Effect of muscular dystrophy caused by PTRF deletion on the transcriptome of skeletal muscles

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