Investigating the regulatory role of KMT2D in neurodeveolopment using organoid and single cell techniques. Investigating the regulatory role of KMT2D in neurodeveolopment using organoid and single cell techniques

Enhancer-mediated gene activation of lineage-specifiers, together with extrinsic niche factors, determines cell fate. Mutations in KMT2D, the H3K4me1-catalyzing enhancer-activator, result in ~70% of the KABUKI syndrome, a neurodevelopmental disorder. Yet the impacted cell-of-origin and the bona fide targets of KMT2D in human neurodevelopment are missing. Here we applied cerebral organoid and single-cell technologies to delineate human-specific distal regulatory elements across heterogeneous cell types. Overall design: We analyzed RNA-seq, CUT&Tag, scRAN-seq, scATAC-seq data of brain organoids differentiated from HN4 cell lines at multiple time points. *** Raw data not submitted due to patient privacy concerns ***

增强子介导的谱系决定因子基因激活，与外源微环境因子共同调控细胞命运。编码H3K4me1催化型增强子激活因子的KMT2D基因突变，可导致约70%的歌舞伎综合征（KABUKI syndrome）——一种神经发育障碍性疾病。然而，在人类神经发育过程中，KMT2D的受损起源细胞及其确凿靶基因仍未明确。本研究利用脑类器官（cerebral organoid）与单细胞技术，解析异质性细胞类型中人类特异性远端调控元件。整体实验设计：我们对多时间点下由HN4细胞系分化得到的脑类器官的RNA测序（RNA-seq）、CUT&Tag、scRAN-seq及scATAC-seq数据进行了分析。*** 受受试者隐私保护相关要求限制，原始数据未提交 ***