瑞士生物系统科学与工程系Barbara Treutlein，Fides Zenk和瑞士巴塞尔罗氏创新中心J. Gray Camp共同合作，近期取得重要工作进展。他们研究绘制了人类神经类器官系统多能性发育轨迹的单细胞表观基因组图谱。相关研究成果2024年6月24日在线发表于《自然—神经科学》杂志上。

据介绍，多能祖细胞的细胞命运进程受到严格调控，导致人类细胞高度多样性。表观遗传学修饰也协调了细胞命运的限制。揭示人类细胞多样性的表观遗传学机制一直很困难。

研究人员使用人脑和视网膜类器官模型，对H3K27ac、H3K27me3和H3K4me3组蛋白从祖细胞到分化神经命运的修饰进行单细胞分析，以重建调节细胞身份获取的表观基因组轨迹。研究人员捕捉了从多能性通过神经上皮到视网膜和大脑区域以及细胞类型规范的转变。抑制性和激活性表观遗传修饰的转换可以先于和预测每个阶段的细胞命运决定，提供基因调控元件和转录因子的时间普查。在神经外胚层阶段去除H3K27me3会破坏命运限制，导致异常的细胞身份获取。

总之，这一研究获取的人类神经类器官发育的单细胞表观基因组图谱，是探索人类细胞命运决定的蓝图。

附：英文原文

Title: Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems

Author: Zenk, Fides, Fleck, Jonas Simon, Jansen, Sophie Martina Johanna, Kashanian, Bijan, Eisinger, Benedikt, Santel, Magorzata, Dupr, Jean-Samuel, Camp, J. Gray, Treutlein, Barbara

Issue&Volume: 2024-06-24

Abstract: Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.

DOI: 10.1038/s41593-024-01652-0

Source: https://www.nature.com/articles/s41593-024-01652-0