Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance [Spatial transcriptome](Dataset ID: STDS0000110)

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Spots: 3,364
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Genes: 32,285
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PMID: 34489413
Summary
Visualization
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Analysis results
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Dataset information
Summary:
Heart disease can be caused by ischemic coronary artery injury, hypertension, and chemotherapy, all of which lead to loss or dysfunction of cardiac muscle. The adult mammalian heart lacks the ability to regenerate. In contrast, the heart of neonatal mice, within the first week after birth, possesses a unique ability to regenerate lost myocardium following injury, mediated by proliferation of cardiomyocytes. The mechanisms whereby neonatal cardiomyocytes adapt to injury-induced stress conditions and activate regenerative cellular programs remain to be defined. Here, we show that Nrf1, an endoplasmic reticulum (ER) bound transcription factor, is expressed in regenerating cardiomyocytes. Genetic deletion of Nrf1 prevented cardiomyocytes from activating a transcriptional program required for heart regeneration, revealed by single-nucleus RNA sequencing (snRNA-seq). Conversely, adeno-associated virial (AAV) overexpression of Nrf1 protected the adult mouse heart from ischemia/reperfusion (I/R) injury. Nrf1 also protected human induced pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) from doxorubicin-induced cardiotoxicity. The protective function of Nrf1 is mediated by a dual stress response mechanism involving activation of the proteasome and redox balance. Our findings reveal a mechanistic interplay between adaptive stress responses and heart regeneration, and highlight the central role of Nrf1 in these processes.
Overall design:
Exmination of transcriptome changes in neonatal rat ventricular cardiomyocytes overexpresing Nrf1 or Nrf2 .
Technology:
10x Visium
Platform:
GPL19057
Species:
Mus musculus(mm10)
Submission date: 2020-12-21Update date: 2021-09-27
Sample number: 5
DOI: To be continue
Contributors
Miao Cui,Ning Liu,Rhonda Bassel-Duby,Eric N Olson
Contact: miaocui713@gmail.com
Accessions
GEO Series Accessions: GSE163629
How to cite
  • Cite database of STOmicsDB:
    [1] Xu, Zhicheng et al. "STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization." Nucleic acids research vol. 52,D1 (2024): D1053-D1061. doi: 10.1093/nar/gkad933'
  • Cite visualization dataset:
    [2] Miao Cui,Ning Liu,Rhonda Bassel-Duby,Eric N Olson. Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance [Spatial transcriptome][DS/OL]. STOmicsDB, 2020[2020-12-21]. https://db.cngb.org/stomics/datasets/STDS0000110/. doi: xxxxxx
    #Format: {contributors}. {title}[DS/OL]. STOmicsDB, {the year of submission data}[{submission data}]. {dataset link}. doi: {doi ID}
  • Cite original data article:
    Citation: Cui, Miao et al. “Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance.” Nature communications vol. 12,1 5270. 6 Sep. 2021, doi:10.1038/s41467-021-25653-w