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Series GSE253383 Query DataSets for GSE253383
Status Public on May 07, 2024
Title Egr1 is a master regulator of regenerative senescence and cardiac repair
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
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.
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
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Submission date Jan 16, 2024
Last update date May 08, 2024
Contact name Jingkui Wang
Organization name Research Institute of Molecular Pathology (IMP)
Lab Tanaka
Street address Campus-Vienna-Biocenter 1
City Vienna
ZIP/Postal code 1030
Country Austria
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM8019516 neonate_d1
GSM8019517 neonate_d4
GSM8019518 neonate_d7
BioProject PRJNA1065443

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Supplementary file Size Download File type/resource
GSE253383_RAW.tar 2.9 Gb (http)(custom) TAR (of MTX, TIFF, TSV)
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Raw data are available in SRA

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