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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

ABSTRACT: Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

PROVIDER: PRJNA955277 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24164000_1.fastq.gz	Fastqsanger.gz
	SRR24164000_2.fastq.gz	Fastqsanger.gz
	SRR24164001_1.fastq.gz	Fastqsanger.gz
	SRR24164001_2.fastq.gz	Fastqsanger.gz
	SRR24164002_1.fastq.gz	Fastqsanger.gz

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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

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Project description:We have generated high-resolution Hi-C map of developing human retinal organoids to elucidate spatiotemporal dynamics of genomic architecture and its relationship with gene expression patterns. We demonstrate progressive and developmental stage-specific alterations in DNA topology and correlate these changes with transcription of cell type-restricted gene markers during retinal differentiation. Temporal Hi-C reveals a shift towards A compartment for protein-coding genes and B compartment for non-coding RNAs, displaying high and low expression respectively. Notably, retina-enriched genes are clustered near lost boundaries of topologically associated domains (TADs), and higher-order assemblages of TADs (i.e., TAD cliques) tend to localize in the active chromatin regions with binding sites for eye-field transcription factors. These genes show a gain of chromatin contacts at their transcription start site as organoid differentiation proceeds. Our study provides a global view of chromatin architecture dynamics associated with diversification of cell types during retinal development and serves as a foundational resource for in-depth functional investigations of retinal developmental traits.

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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

Project description:This SuperSeries is composed of the SubSeries listed below. We have generated high-resolution Hi-C map of developing human retinal organoids to elucidate spatiotemporal dynamics of genomic architecture and its relationship with gene expression patterns. We demonstrate progressive and developmental stage-specific alterations in DNA topology and correlate these changes with transcription of cell type-restricted gene markers during retinal differentiation. Temporal Hi-C reveals a shift towards A compartment for protein-coding genes and B compartment for non-coding RNAs, displaying high and low expression respectively. Notably, retina-enriched genes are clustered near lost boundaries of topologically associated domains (TADs), and higher-order assemblages of TADs (i.e., TAD cliques) tend to localize in the active chromatin regions with binding sites for eye-field transcription factors. These genes show a gain of chromatin contacts at their transcription start site as organoid differentiation proceeds. Our study provides a global view of chromatin architecture dynamics associated with diversification of cell types during retinal development and serves as a foundational resource for in-depth functional investigations of retinal developmental traits.

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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids.

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