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| Status |
Public on Oct 11, 2022 |
| Title |
Muscle injury induces a transient senescence-like state that is required for myofiber growth during muscle regeneration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cellular senescence is the irreversible arrest of normally dividing cells and is driven by the cell cycle inhibitors Cdkn2a, Cdkn1a, and Trp53. Senescent cells are implicated in chronic diseases and tissue repair through their increased secretion of proinflammatory factors known as the senescence-associated secretory phenotype (SASP). Here, we use spatial transcriptomics and single-cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are “transiently" present within regenerating skeletal muscle and within the muscles of D2-mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibro-adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence-associated beta-gal (SA-β-gal) activity. Importantly, when these cells were removed with ABT-263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion.
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| Overall design |
Tibialis anterior muscle were collected from C57BL/6 mice 5 days post-CTX or PBS injection (n = 5 mice for each group) and then pooled following dissociation into single cells. Single-cell RNA-sequencing (scRNA-seq) was performed using 10x Genomics Chromium Single Cell 3' platform (v3).
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| Contributor(s) |
Young LV, Wakelin GM, Johnston AP |
| Citation(s) |
36190443 |
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| Submission date |
Oct 05, 2022 |
| Last update date |
Oct 13, 2022 |
| Contact name |
Adam Johnston |
| E-mail(s) |
[email protected]
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| Organization name |
Dalhousie University
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| Department |
Medical Neuroscience
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| Lab |
Johnston Lab
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| Street address |
1344 Summer Street
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| City |
Halifax |
| State/province |
NS |
| ZIP/Postal code |
B3H0A8 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA887476 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE214892_RAW.tar |
87.6 Mb |
(http)(custom) |
TAR (of TAR) |
| GSE214892_seu.rds.gz |
834.4 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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