德国慕尼黑大学Boyan Bonev团队发现，联合表观基因组图谱揭示人类大脑皮质类器官组织中细胞类型特异性基因调控方案。2023年11月23日，《自然—细胞生物学》期刊在线发表了这一成果。

研究人员描述了一种方法：三维基因组、RNA、可及性和甲基化测序（3DRAM-seq），它能同时以高分辨率检测全基因组的空间基因组组织、染色质可及性和DNA甲基化。研究人员将3DRAM-seq与皮质类器官组织中的免疫FACS和RNA测序结合起来，绘制出跨多个表观遗传层的人类神经发育的细胞类型特异性调控图谱。最后，研究人员应用大规模并行报告分析法来描述了类器官组织中细胞类型特异性增强子的活性，并从功能上评估关键转录因子在人类增强子激活和功能中的作用。更广泛地说，3DRAM-seq可用于描述稀有细胞类型和不同组织的多模式表观遗传景观。

据了解，基因表达受多种表观遗传机制调控，这些机制在发育和疾病过程中相互协调。然而，目前的多组学方法往往仅限于一种或两种模式，这使得获得全面的基因调控特征具有挑战性。

附：英文原文

Title: Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids

Author: Noack, Florian, Vangelisti, Silvia, Ditzer, Nora, Chong, Faye, Albert, Mareike, Bonev, Boyan

Issue&Volume: 2023-11-23

Abstract: Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a comprehensive gene regulatory signature. Here, we describe a method—3D genome, RNA, accessibility and methylation sequencing (3DRAM-seq)—that simultaneously interrogates spatial genome organization, chromatin accessibility and DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA sequencing in cortical organoids to map the cell-type-specific regulatory landscape of human neural development across multiple epigenetic layers. Finally, we apply a massively parallel reporter assay to profile cell-type-specific enhancer activity in organoids and to functionally assess the role of key transcription factors for human enhancer activation and function. More broadly, 3DRAM-seq can be used to profile the multimodal epigenetic landscape in rare cell types and different tissues.

DOI: 10.1038/s41556-023-01296-5

Source: https://www.nature.com/articles/s41556-023-01296-5