Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB12200 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR317298_1.fastq.gz | Fastqsanger.gz | |||
| DRR317298_2.fastq.gz | Fastqsanger.gz | |||
| DRR317299_1.fastq.gz | Fastqsanger.gz | |||
| DRR317299_2.fastq.gz | Fastqsanger.gz | |||
| DRR317300_1.fastq.gz | Fastqsanger.gz |
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Project description:Heart failure is associated with high mortality rates and reduced quality of life. Because of the tight connection between Nppa expression and cardiomyocyte stress, we first determined NPPA correlated genes during heart failure. In this study, we identify SORBS2 as conserved NPPA correlated gene and detail its molecular function and association with heart failure. We used RNA-sequencing on murine whole heart tissue to study the effect of cardiomyocyte-specific genetic loss of Sorbs2 in adult mice in a healthy situation and heart failure model.
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Project description:Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
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Project description:Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
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Project description:To illustrate the immune cell atlas and functional heterogeneity of T cell repertoire in murine heart transplantation，we established the murine heterotopic heart transplantation model and isolated CD45 positive cells from cardiac grafts and spleens for single cell transcriptome and TCR sequencing.
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