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A Comparative Assessment of iPSC Derived Cardiomyocytes with Heart Tissues in Humans and Chimpanzees

ABSTRACT: A Comparative Assessment of iPSC Derived Cardiomyocytes with Heart Tissues in Humans and Chimpanzees

PROVIDER: PRJNA433831 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6706630.fastq.gz	Fastqsanger.gz
	SRR6706640.fastq.gz	Fastqsanger.gz
	SRR6706650.fastq.gz	Fastqsanger.gz
	SRR6706660.fastq.gz	Fastqsanger.gz
	SRR6706670.fastq.gz	Fastqsanger.gz

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A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

Project description:Despite anatomical similarities, there are differences in susceptibility to cardiovascular disease (CVD) between primates; humans are prone to myocardial ischemia, while chimpanzees are prone to myocardial fibrosis. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) allow for direct inter-species comparisons of the gene regulatory response to CVD-relevant perturbations such as oxygen deprivation, a consequence of ischemia. To gain insight into the evolution of disease susceptibility, we characterized gene expression levels in iPSC-CMs in humans and chimpanzees, before and after hypoxia and re-oxygenation. The transcriptional response to hypoxia is generally conserved across species, yet we were able to identify hundreds of species-specific regulatory responses including in genes previously associated with CVD. The 1,920 genes that respond to hypoxia in both species are enriched for loss-of-function intolerant genes; but are depleted for expression quantitative trait loci and cardiovascular-related genes. Our results indicate that response to hypoxic stress is highly conserved in humans and chimpanzees.

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A Comparative Assessment of iPSC Derived Cardiomyocytes with Heart Tissues in Humans and Chimpanzees

Project description:To study regulatory differences between species, the field of comparative primate genomics has used several approaches, including the use of post mortem frozen tissues, cell lines, and model organisms. However, there are limited quality cell lines from primates and post-mortem tissues cannot be staged, are not amenable to experimental perturbations and are often subject to high environmental variances. Inducible pluripotent stem cells (iPSCs) are an attractive system to study primate biology in a comparative context. However, the fidelity of iPSC derived cell types to primary tissues needs to be assayed in a comparative primate context before the utility of iPSCs can be fully realized for comparative genomics. In order to comprehensively benchmark the performance of iPSC model systems in a comparative framework, we collected RNA-sequencing from primary adult heart tissue and iPSC derived cardiomyocytes from multiple human and chimpanzee individuals. We identified the optimal parameters of iPSC differentiation into cardiomyocytes that minimized differences between each species and their respective adult tissue counterparts in a balanced manner across species. We found that iPSC derived cardiomyocytes are able to recapitulate 50% of the interspecies gene expression differences identified between human and chimpanzee in primary post mortem heart tissues. Furthermore, we determined that cultured cardiomyocytes appear more similar to adult hearts than any other single tissue in their ability to recapitulate differences in gene regulation between human and chimpanzee.

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