Chromatin Accessibility Analysis Reveals Regulatory Dynamics in hESC-Derived Kidney Organoids [ATAC-seq]

Kidney organoid model can better simulate the development process, thereby providing an optimal platform for elucidating the mechanisms underlying human kidney development. In this study, we systematically characterized the chromatin availability dynamics and transcriptional regulation during the induction of human embryonic stem cells (hESCs) into kidney organoids (E-iKOs) for the first time. We demonstrated that HNF1B is essential for nephrogenesis, as its deficiency results in absence of tubule structures. Furthermore, DOT1L, a histone H3K79 methyltransferase, is activated during E-iKOs induction and is predominantly responsible for opening pivotal loci and promotes the mesenchymal to epithelial transition (MET) required for kidney epithelial differentiation. Collectively, our study provides valuable resources and insights into the mechanistic study of human kidney development in vitro at the chromatin remodeling level.