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| Status |
Public on May 07, 2024 |
| Title |
Egr1 regulates regenerative senescence and cardiac repair |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA-sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and Agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, Agrin-induced senescence and repair require Egr1, activated by the integrin/FAK-ERK/Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype (SASP) components that promote ECM degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.
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| Overall design |
Hearts from postnatal day 1 mice were subjected to cryoinjury and were harvested at 1,4,7 and 14 day after injury. The hearts were harvested and flesh frozen for spatial transcriptomics. Hearts were sectioned until injured area was apparant and then prepd for downstream pipeline.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/39196027/
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| Contributor(s) |
Zhang L, Elkahal J, Wang T, Rimmer R, Genzelinakh A, Bassat E, Wang J, Perez D, Kain D, Lendengolts D, Winkler R, Bueno-levy H, Umansky KB, Mishaly D, Shakked A, Miyara S, Goldfinger N, Prior A, Morgenstern D, Levin Y, Addadi Y, Li B, Rotter V, Krizhanovsky V, Katz U, Tanaka EM, Sarig R, Tzahor E |
| Citation(s) |
39196027 |
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| Submission date |
Jan 16, 2024 |
| Last update date |
Sep 04, 2024 |
| Contact name |
Jingkui Wang |
| E-mail(s) |
jingkui.wang@imp.ac.at
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| Organization name |
Research Institute of Molecular Pathology (IMP)
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| Lab |
Tanaka
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| Street address |
Campus-Vienna-Biocenter 1
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| City |
Vienna |
| ZIP/Postal code |
1030 |
| Country |
Austria |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1065443 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253383_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of MTX, TIFF, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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