小柯机器人

美国纽约基因组中心Rahul Satija研究团队利用scCUT&Tag-pro揭示细胞染色质状态的异质性。2022年3月24日，国际知名学术期刊《自然—生物技术》在线发表了这一成果。

研究人员介绍了单细胞(sc)CUT&Tag-pro，这是一种多模式的检测方法，用于分析蛋白质与DNA的相互作用以及单细胞中表面蛋白的丰度。此外，研究人员还介绍了单细胞ChromHMM，它整合了多个实验的数据，根据组合组蛋白修饰模式推断和注释染色质状态。研究人员应用这些工具对循环中的人类免疫细胞的九个不同的分子模式进行了综合分析。

研究人员展示了这两种方法如何在离散的细胞状态和连续的发育轨迹中描述单个基因组元素功能的动态变化，发现了建立染色质状态的相关模体和调节因子，并确定了广泛的和细胞类型特定的调控活化。最后，研究人员展示了这个综合参考是如何作为一个支架来映射和改善其他scCUT&Tag数据集的解释。

据介绍，在单细胞分辨率下剖析染色质修饰的技术为功能基因组表征提供了巨大的希望，但测量的稀疏性和整合多种结合图谱是巨大的挑战。

附：英文原文

Title: Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro

Author: Zhang, Bingjie, Srivastava, Avi, Mimitou, Eleni, Stuart, Tim, Raimondi, Ivan, Hao, Yuhan, Smibert, Peter, Satija, Rahul

Issue&Volume: 2022-03-24

Abstract: Technologies that profile chromatin modifications at single-cell resolution offer enormous promise for functional genomic characterization, but the sparsity of the measurements and integrating multiple binding maps represent substantial challenges. Here we introduce single-cell (sc)CUT&Tag-pro, a multimodal assay for profiling protein–DNA interactions coupled with the abundance of surface proteins in single cells. In addition, we introduce single-cell ChromHMM, which integrates data from multiple experiments to infer and annotate chromatin states based on combinatorial histone modification patterns. We apply these tools to perform an integrated analysis across nine different molecular modalities in circulating human immune cells. We demonstrate how these two approaches can characterize dynamic changes in the function of individual genomic elements across both discrete cell states and continuous developmental trajectories, nominate associated motifs and regulators that establish chromatin states and identify extensive and cell-type-specific regulatory priming. Finally, we demonstrate how our integrated reference can serve as a scaffold to map and improve the interpretation of additional scCUT&Tag datasets.

DOI: 10.1038/s41587-022-01250-0

Source: https://www.nature.com/articles/s41587-022-01250-0

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