Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (snATAC-Seq). Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (snATAC-Seq)

ENL is an epigenetic acetylation reader and represents the most frequently mutated epigenetic regulator in Wilms tumor. In this study, we established an in vivo mouse model with the ENL hotspot mutation Enl-T1. We performed single-nuclei ATAC sequencing (snATAC-seq) analysis for the Enl-WT and T1 embryonic kidney to study the open chromatin dynamics and gene regulatory mechanism underlying the kidney developing defeat induced by the Enl mutation. Overall design: E15.5 kidneys with or without Enl-T1 mutation from B6 mice were isolated for the scRNA-seq assays, followed by corresponding analysis.

ENL是一种表观遗传乙酰化阅读器，同时是肾母细胞瘤（Wilms tumor）中突变频率最高的表观遗传调控因子。本研究构建了携带ENL热点突变Enl-T1的体内小鼠模型。我们对Enl野生型（Enl-WT）及T1突变胚胎肾脏开展了单细胞核ATAC测序（single-nuclei ATAC sequencing, snATAC-seq）分析，以探究Enl突变诱导的肾脏发育缺陷背后的开放染色质动态变化与基因调控机制。实验设计概述：分离来自B6小鼠的、携带或不携带Enl-T1突变的胚胎发育第15.5天（E15.5）肾脏，开展单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）实验并进行后续相关分析。