瑞典卡罗林斯卡学院Gonçalo Castelo-Branco和斯德哥尔摩大学Marek Bartosovic团队合作的最新研究，利用基于纳米抗体的单细胞CUT&Tag完成对多模式染色质分析。2022年12月19日出版的《自然-生物技术》杂志发表了这项成果。
研究人员研发了nano-CUTTag（nano-CT），它利用纳米抗体-Tn5融合蛋白以单细胞分辨率同时映射多达三种表观基因组模式。多模态nano-CT可适用于低至25，000-200，000个细胞的起始样本，并且每个细胞的灵敏度和片段数量明显高于单细胞CUTTag。研究人员利用Nano-CT同时分析幼年小鼠大脑中质的可及性、H3K27ac和H3K27me3，可区分比单峰单细胞CUTTag更多的细胞类型和状态。
研究人员检测了少突胶质细胞谱系中转座酶所在染色质（ATAC）与H3K27ac之间的染色质速度。研究人员还检测了去卷积H3K27me3抑制状态发现在少突胶质细胞谱系发育期间在不同基因模块处发现了两波连续的H3K27me3抑制。鉴于其高分辨率、多功能性和多模态特性，nano-CT可以在单细胞水平上对复杂生物系统的表观遗传图谱进行解析。
据介绍，单细胞CUTTag等技术可实现在数千个细胞中检测单细胞水平的组蛋白修饰。
附：英文原文
Title: Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag
Author: Bartosovic, Marek, Castelo-Branco, Gonalo
Issue&Volume: 2022-12-19
Abstract: Probing histone modifications at a single-cell level in thousands of cells has been enabled by technologies such as single-cell CUT&Tag. Here we describe nano-CUT&Tag (nano-CT), which allows simultaneous mapping of up to three epigenomic modalities at single-cell resolution using nanobody-Tn5 fusion proteins. Multimodal nano-CT is compatible with starting materials as low as 25,000–200,000 cells and has significantly higher sensitivity and number of fragments per cell than single-cell CUT&Tag. We use nano-CT to simultaneously profile chromatin accessibility, H3K27ac, and H3K27me3 in juvenile mouse brain, allowing for discrimination of more cell types and states than unimodal single-cell CUT&Tag. We also infer chromatin velocity between assay for transposase-accessible chromatin (ATAC) and H3K27ac in the oligodendrocyte lineage and deconvolute H3K27me3 repressive states, finding two sequential waves of H3K27me3 repression at distinct gene modules during oligodendrocyte lineage progression. Given its high resolution, versatility, and multimodal features, nano-CT allows unique insights in epigenetic landscapes in complex biological systems at the single-cell level.
DOI: 10.1038/s41587-022-01535-4
Source: https://www.nature.com/articles/s41587-022-01535-4
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
本期文章：《自然—生物技术》：Online/在线发表
