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Single-cell RNA-sequencing reveals the effects of right ventricular volume overload on cardiomyocyte proliferation via immune responses

ABSTRACT: Single-cell RNA-sequencing reveals the effects of right ventricular volume overload on cardiomyocyte proliferation via immune responses

PROVIDER: PRJNA1073434 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27872677_1.fastq.gz	Fastqsanger.gz
	SRR27872677_2.fastq.gz	Fastqsanger.gz
	SRR27872678_1.fastq.gz	Fastqsanger.gz
	SRR27872678_2.fastq.gz	Fastqsanger.gz
	SRR27872679_1.fastq.gz	Fastqsanger.gz

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Effect of volume overload on right ventricular remodeling in neonatal SD rats

Project description:We reported the RNAseq analyses of right ventricualr free wall myocardium in neonatal volume overload (VO) SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV free wall at P7 from VO and sham-operated rat revealed that there were 454 differentially expressed genes between VO and sham group at P7. GO analysis showed that in the VO and sham comparison, the upregulated genes mainly mediated immune system response and the downregulated genes mainly mediated apoptotic process at P7. VO has no effect to neonatal right ventricular cardiomyocyte proliferation.

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Cyclosporin ameliorates right ventricular remodeling of postnatal mice with volume overload.

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Cyclosporin ameliorates right ventricular remodeling of postnatal mice with volume overload.

Project description:We reported the RNAseq analyses of right ventricular free wall of myocardium in three groups of mice（3 in each group）at postnatal day 14 (P14). The mice in volume overload (VO) group underwent an abdominal surgery by puncture from aorta to inferior vena cava at P7, mice in Sham group underwent the same surgery except for the puncture. The mice in CsA group were VO mice who were also injected with cyclosporin A(CsA) for seven days. The results revealed that there were differentially expressed genes between VO and sham group at P14, Inhibiting the immune response with CsA caused the gene expression profile of VO mice to shift towards that of sham mice.

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Transcriptional characterization of cardiomyocyte nuclei from neonatal mice with volume overload

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Single-cell RNA-sequencing reveals the effects of right ventricular volume overload on cardiomyocyte proliferation via immune responses

Project description:Background: Right ventricular volume overload (RVVO) is one of the most important hemodynamic characteristics in children with congenital heart diseases (CHDs) and heart failure, and cardiomyocyte (CM) proliferation is a vital factor for improving cardiac performance. However, whether and how RVVO reboots CM proliferation remains elusive. Methods and Results: We first created a prepubertal RVVO mouse model by an abdominal- aorta- and inferior- vena- cava- fistula (ACF) surgery on postnatal day 7(P7). Then we performed bulk RNA-seq on RVs of RVVO mice on P14, which showed that the top 30 enriched gene ontology(GO) terms of upregulated genes were associated with cell proliferation and that cell cycle was the fourth top enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway terms. Immunofluorescence staining confirmed the results, showing significantly increased numbers of phosphorylated histone 3/Aurora B-positive CMs in RVs with RVVO when compared to those in control RVs. Single RNA-seq performed on P21 further confirmed the results, showing increased percentage of CMs, with five sub-functional CMs, in which immature CMs increased while mature CMs decreased. In addition, RNA-seq/flow cytometry demonstrated that RVVO induced an immune response. Inhibiting the immune response with cyclosporin A(CsA) caused the gene expression profile of RVVO mice to shift towards that of sham mice, with a significant decrease in cell cycle associated genes’ enrichment. Conclusions: RVVO temporarily reboots prepubertal CM proliferation via immune responses. This study may provide an opportunity to create a novel paradigm to treat pediatric CHDs or heart failure in considering the importance of RVVO and CM proliferation in CHDs or heart failure.

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Project description:The Right Ventricular Fibroblast Secretome Drives Cardiomyocyte Dedifferentiation

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Pressure overload greatly promotes neonatal right ventricular cardiomyocyte proliferation - a new model for heart regeneration study

Project description:Pressure overload greatly promotes neonatal right ventricular cardiomyocyte proliferation - a new model for heart regeneration study

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