摘要：Endogenous DNA double-strand breaks (DSBs) occurring in neural cells have been implicated in the pathogenesis of neurodevelopmental disorders (NDDs) . Currently, a genomic map of endogenous DSBs arising during human neurogenesis is missing . Here, we applied in-suspension Breaks Labeling In Situ and Sequencing (sBLISS), RNA-Seq, and Hi-C to chart the genomic landscape of DSBs and relate it to gene expression and genome architecture in 2D cultures of human neuroepithelial stem cells (NES), neural progenitor cells (NPC), and post-mitotic neural cells (NEU) . Endogenous DSBs were enriched at the promoter and along the gene body of transcriptionally active genes, at the borders of topologically associating domains (TADs), and around chromatin loop anchors . NDD risk genes harbored signifcantly more DSBs in comparison to other protein-coding genes, especially in NEU cells . We provide sBLISS, RNA-Seq, and Hi-C datasets for each diferentiation stage, and all the scripts needed to reproduce our analyses . Our datasets and tools represent a unique resource that can be harnessed to investigate the role of genome fragility in the pathogenesis of NDDs .
