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Spatial transcriptomics reveals expression of novel genes during the remodelling of the embryonic human heart

ABSTRACT: Spatial transcriptomics reveals expression of novel genes during the remodelling of the embryonic human heart

PROVIDER: PRJNA1024449 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26297583_1.fastq.gz	Fastqsanger.gz
	SRR26297583_2.fastq.gz	Fastqsanger.gz
	SRR26297584_1.fastq.gz	Fastqsanger.gz
	SRR26297584_2.fastq.gz	Fastqsanger.gz
	SRR26297585_1.fastq.gz	Fastqsanger.gz

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Project description:Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST). We show that ST can be used to investigate the transcriptome of the developing arterial valves, circumventing the problems of accurately dissecting out these tiny structures from the developing embryo. We show that the transcriptome of CS16 and CS19 arterial valves overlap considerably, despite being several days apart in terms of human gestation, and that expression data confirm that the great majority of the most differentially expressed genes are valve-specific. Moreover, we show that the transcriptome of the human arterial valves overlaps with that of mouse atrioventricular valves from a range of gestations, validating our dataset but also highlighting novel genes, including four that are not found in the mouse genome and have not previously been linked to valve development. Importantly, our data suggests that valve transcriptomes are under-represented when using commonly used databases to filter for genes important in cardiac development; this means that causative variants in valve-related genes may be excluded during filtering for genomic data analyses for, for example, BAV. Finally, we highlight "novel" pathways that likely play important roles in arterial valve development, showing that mouse knockouts of RBP1 have arterial valve defects. Thus, this study has confirmed the utility of ST for studies of the developing heart valves and broadens our knowledge of the genes and signalling pathways important in human valve development.

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Spatial transcriptomics reveals expression of novel genes during the remodelling of the embryonic human heart

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