小柯机器人

瑞典卡洛琳卡学院Gonçalo Castelo-Branco、Marek Bartosovic等研究人员合作发现，单细胞CUT＆Tag可分析复杂组织中的组蛋白修饰和转录因子。相关论文于2021年4月12日在线发表在《自然—生物技术》杂志上。

研究人员将为测量大量组蛋白修饰而开发的CUT＆Tag技术与基于液滴的单细胞文库制备相结合，来获得了有关染色质修饰的高质量单细胞数据。研究人员将单细胞CUT＆Tag（scCUT＆Tag）应用于小鼠中枢神经系统的成千上万个细胞，并探查了活跃启动子、增强子和基因体（H3K4me3、H3K27ac和H3K36me3）和非活性区（H3K27me3）的组蛋白修饰特征。这些scCUT＆Tag图谱足以确定细胞身份和反卷积揭示调节原理，例如启动子双价、H3K4me3的扩散和启动子-增强子的连接性。

研究人员还使用了scCUT＆Tag来研究转录因子OLIG2和黏连蛋白复合物成分RAD21在单细胞染色质中的占据。这些结果表明，在单细胞分辨率下对组蛋白修饰和转录因子占据的分析提供了对中枢神经系统表观基因组图谱的独特见解。

据悉，与用于测量基因表达和DNA可及性的单细胞方法相比，用于分析组蛋白修饰的单细胞方法受到低灵敏度和高通量的限制。

附：英文原文

Title: Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues

Author: Marek Bartosovic, Mukund Kabbe, Gonalo Castelo-Branco

Issue&Volume: 2021-04-12

Abstract: In contrast to single-cell approaches for measuring gene expression and DNA accessibility, single-cell methods for analyzing histone modifications are limited by low sensitivity and throughput. Here, we combine the CUT&Tag technology, developed to measure bulk histone modifications, with droplet-based single-cell library preparation to produce high-quality single-cell data on chromatin modifications. We apply single-cell CUT&Tag (scCUT&Tag) to tens of thousands of cells of the mouse central nervous system and probe histone modifications characteristic of active promoters, enhancers and gene bodies (H3K4me3, H3K27ac and H3K36me3) and inactive regions (H3K27me3). These scCUT&Tag profiles were sufficient to determine cell identity and deconvolute regulatory principles such as promoter bivalency, spreading of H3K4me3 and promoter–enhancer connectivity. We also used scCUT&Tag to investigate the single-cell chromatin occupancy of transcription factor OLIG2 and the cohesin complex component RAD21. Our results indicate that analysis of histone modifications and transcription factor occupancy at single-cell resolution provides unique insights into epigenomic landscapes in the central nervous system.

DOI: 10.1038/s41587-021-00869-9

Source: https://www.nature.com/articles/s41587-021-00869-9

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex