EXPERIMENT_TITLE: Hi-C performed on NPC cells (replicate 2)
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Naturally occurring endogenous DNA double-strand breaks (DSBs) have been detected in neuronal cells and implicated in the pathogenesis of neurodevelopmental disorders (NDDs). Here, we describe a genome-wide atlas of endogenous DSBs mapped by suspension Breaks Labeling In Situ and Sequencing (sBLISS) in proliferating neuroepithelial stem (NES) cells in culture, neural progenitor cells (NPC) after 6 days of NES differentiation towards neurons, and post-mitotic neurons (NEU) after 35 days of differentiation. Genome-wide DSB maps were highly reproducible between biological replicates of the same cell type, at multiple resolutions down to 10 kilobases (kb). To validate our datasets, we examined the distribution of DSBs in different genomic regions, demonstrating that endogenous DSBs are enriched around transcriptionally active promoters and chromatin loop anchors mapped by high-throughput chromosome conformation capture (Hi-C), in line with previous findings in different cell types. Lastly, we assessed DSBs in the promoter region and along the gene body of NDD risk genes, demonstrating that these genes have a significantly higher burden of DSBs compared to all other genes in all the three cell types examined, confirming prior observations using different DSB-detection strategies. Our datasets represent a valuable resource for exploring genome fragility during neural cell fate determination and assessing its contribution to the pathogenesis of neurodevelopmental disorders.
SAMPLE_TITLE: NPC - Hi-C - rep2
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "isolate", "VALUE": "NA"}, {"TAG": "age", "VALUE": "NA"}, {"TAG": "biomaterial_provider", "VALUE": "KI IPS cell core facility, Stockholm, Sweden"}, {"TAG": "sex", "VALUE": "female"}, {"TAG": "tissue", "VALUE": "NA"}, {"TAG": "cell_line", "VALUE": "AF22 lt-NES cells"}, {"TAG": "cell_subtype", "VALUE": "Neural progenitor cells"}, {"TAG": "cell_type", "VALUE": "iPS cell-derived lt-NES cells differentiated for 6 days"}, {"TAG": "replicate", "VALUE": "2"}, {"TAG": "sequencing_type", "VALUE": "Hi-C"}, {"TAG": "BioSampleModel", "VALUE": "Human"}]
Pool_Member_@attributes_sample_title: NPC - Hi-C - rep2
RUN_SET_RUN_Pool_Member_@attributes_sample_title: NPC - Hi-C - rep2
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