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Integrated genomic and proteomic analyses identify stimulus-dependent distinct molecular changes associated with skeletal muscle wasting

ABSTRACT: Integrated genomic and proteomic analyses identify stimulus-dependent distinct molecular changes associated with skeletal muscle wasting

PROVIDER: PRJNA670942 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12884465_1.fastq.gz	Fastqsanger.gz
	SRR12884465_2.fastq.gz	Fastqsanger.gz
	SRR12884466_1.fastq.gz	Fastqsanger.gz
	SRR12884466_2.fastq.gz	Fastqsanger.gz
	SRR12884467_1.fastq.gz	Fastqsanger.gz

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Integrated genomic and proteomic analyses identify stimulus-dependent distinct molecular changes associated with skeletal muscle wasting

Project description:Skeletal muscle wasting is a debilitating condition that occurs with aging and with many diseases, but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in skeletal muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer, and aging) induce largely different mRNA and protein changes during muscle wasting in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from these proteomic surveys as the most relevantly associated with atrophy. Based on these analyses, we identify atrophy-regulated proteins (here defined as “atroproteins”) such as the myokine CCN1/Cyr61, which we find regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle wasting via largely distinct mechanisms.

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Integrated genomic and proteomic analyses identify stimulus-dependent molecular changes associated with distinct modes of skeletal muscle atrophy.

Project description:Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from proteomics as generally induced by atrophy. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as "atroproteins") such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms.

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Integrated genomic and proteomic analyses identify stimulus-dependent molecular changes associated with distinct modes of skeletal muscle atrophy

Project description:Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from these proteomic surveys as the most relevantly associated with atrophy in all conditions. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as “atroproteins”) such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms.

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