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Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE163631 | GEO | 2021/05/01

REPOSITORIES: GEO

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Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance.

Project description: Not available

| S-EPMC8421386 | biostudies-literature

Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance [scRNA-Seq]

Project description: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.

2021-05-01 | GSE163630 | GEO

Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance [bulkRNA-Seq]

2021-05-01 | GSE163628 | GEO

Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance [Spatial transcriptome]

2021-05-01 | GSE163629 | GEO

Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance

Project description:Ten million neonatal rat ventricular cardiomyocytes were infected with adenovirus to overexpress NRF1 or LacZ (control). 48 hours after infection, cells were collected and lysed for TMT proteomic analysis.

2021-04-13 | MSV000087183 | MassIVE