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Arid1a is essential in cardiomyocytes for neonatal heart maturation

ABSTRACT: Arid1a is essential in cardiomyocytes for neonatal heart maturation

PROVIDER: PRJNA648412 | ENA |

REPOSITORIES: ENA

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Arid1a is essential in cardiomyocytes for neonatal heart maturation [ChIP-seq]

Project description:Adult mammalian hearts do not regenerate following ischemic injury, causing permanent damage to the myocardium, often leading to heart failure. In contrast, neonatal mouse hearts can fully regenerate after injury, however this ability is lost shortly after birth. Loss of regenerative capacity coincides with profound changes in the epigenetic landscape. Yet, the mechanisms controlling cardiomyocyte proliferation remain poorly understood. To identify epigenetic mechanisms that underlie cardiomyocyte regeneration in response to ischemic injury, we subjected mice to sham or ischemia-reperfusion injury (IR) and performed RNA-Seq at multiple timepoints after injury. Multiple SWI/SNF chromatin remodeling complex subunits were upregulated after IR, including the AT-rich interactive domain-containing protein 1A (Arid1a), which has previously been implicated in tissue regeneration. Here, we show that Arid1a is abundantly expressed in cardiomyocytes during development, and is reactivated in a subset of adult cardiomyocytes after IR. Moreover, ARID1A is highly expressed in cardiomyocytes in human failing hearts, suggesting an important function in injury response. Cardiomyocyte-specific Arid1a ablation in neonatal mice induced cardiomyocyte hyperplasia, and severe cardiac enlargement at 2 weeks of age. Arid1a mutant hearts display increased expression of key cell cycle genes. Using ChIP-Seq and protein interaction studies we show that Arid1a functionally interacts with HIPPO signaling, thereby regulating neonatal cardiomyocyte proliferation. Furthermore, suppression of Arid1a in adult cardiomyocytes after IR induced cell cycle activity in border zone cardiomyocytes. These data suggest that Arid1a regulates cardiomyocyte proliferation and function. Upregulation of Arid1a in cardiomyocytes after injury may suppress proliferation and regeneration. Modulation of ARID1A after ischemic injury may be a novel therapeutic target to enhance cardiac regeneration.

2023-07-06 | GSE155100 | GEO

Arid1a is essential in cardiomyocytes for neonatal heart maturation [RNA-seq]

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Arid1a is essential in cardiomyocytes for neonatal heart maturation [RNA-seq]

Project description:Arid1a is essential in cardiomyocytes for neonatal heart maturation [RNA-seq]

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Arid1a is essential in cardiomyocytes for neonatal heart maturation [ChIP-seq]

Project description:Arid1a is essential in cardiomyocytes for neonatal heart maturation [ChIP-seq]

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Arid1a is essential in cardiomyocytes for neonatal heart maturation

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-05 | GSE155102 | GEO

αKG treatment prevent maturation and stimulate proliferation of neonatal cardiomyocytes

Project description:αKG treatment prevent maturation and stimulate proliferation of neonatal cardiomyocytes

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Neonatal Heart Maturation (NHM) SuperSeries GSE85728

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Gene expression profiles of neonatal cardiomyocytes and immortalized heart muscle cells exposed to inflammatory stimuli

Project description:We used a transcriptomic approach to systematically compare the response to inflammatory stimuli for two murine cardiomyocyte models. Our results indicate that murine neonatal cardiomyocytes (NNC) are able to exhibit a pronounced response upon inflammatory stimuli, while HL-1 cells were predominantly recruiting transcripts corresponding to Jak-Stat-signalling. RNA from murine HL-1 cardiomyocytes and isolated neonatal cardiomyocytes (NNC) stimulated by infectious (PCI) serum or LPS or a cytokine mix (CM) were extracted (n=4 each group) and subjected to microarray analysis for comparison of transcriptomic responses.

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MicroRNA expression in neonatal and adult rat cardiomyocytes

Project description:Expression profiles of microRNAs in neonatal (isolated from day0 newborn rats) and adult rat cardiomyocytes (isolated from 2month old rats) Two condition experiment; Biological replicates: 7 samples of cardiomyocytes from neonatal rats (from independent isolations); 6 samples of cardiomyocytes isolated from adult animals (from independent isolations)

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Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

Project description:Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

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