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| Status |
Public on Jul 12, 2024 |
| Title |
A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single nucleus resolution [snATAC] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-induced gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. shRNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of cancer cachexia-induced muscle atrophy and highlight potential therapeutic targets for this disorder.
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| Overall design |
Comparative gene expression profiling analysis of single nucleus RNA-seq data for three biological replicates of Gastrocnemius-plantaris (GP) muscles from control and a mouse model with cancer cachexia (KIC) at 66 days of age.
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| Contributor(s) |
Zhang Y, Dos Santos M, Chen K, Xu L |
| Citation missing |
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| Submission date |
Jul 12, 2024 |
| Last update date |
Jul 13, 2024 |
| Contact name |
kenian chen |
| E-mail(s) |
chenkn007@gmail.com
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| Organization name |
UTsouthwestern
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| Department |
Population and Data Science
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| Lab |
Quantitative Biological Research Center
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| Street address |
5323 Harry Hines Boulevard
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1135089 |
