Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression.
Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression.
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DOI：
10.1038/s41587-021-00865-z
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发表时间：
2021-07
影响因子：
46.9
通讯作者：
Patel AP
中科院分区：
文献类型：
--
作者：
Wu SJ;Furlan SN;Mihalas AB;Kaya-Okur HS;Feroze AH;Emerson SN;Zheng Y;Carson K;Cimino PJ;Keene CD;Sarthy JF;Gottardo R;Ahmad K;Henikoff S;Patel AP
定量单细胞中基因表达和染色质可及性的方法已经建立，但单细胞分析具有特定组蛋白修饰的染色质区域在技术上具有挑战性。在这项研究中，我们将CUT&Tag方法应用于可扩展的纳米孔和基于液滴的单细胞平台，以分析来自复杂组织的单细胞（scCUT&Tag）和人类胚胎干细胞分化过程中的染色质景观。我们专注于分析单细胞中由组蛋白H3 Lys27三甲基化（H3K27me3）标记的多梳组（PcG）沉默区，作为鉴定细胞状态的染色质可及性的正交方法。我们发现H3K27me3的scCUT&Tag分析可以区分人类血液中的细胞类型，并允许从异质组织中产生细胞类型特异性的PcG景观。此外，我们使用scCUT&Tag对一名脑肿瘤患者治疗前后的H3K27me3进行了分析，确定了肿瘤微环境中的细胞类型以及原发性样本和治疗后PcG活性的异质性。
Methods for quantifying gene expression and chromatin accessibility in single cells are well established, but single-cell analysis of chromatin regions with specific histone modifications has been technically challenging. In this study, we adapted the CUT&Tag method to scalable nanowell and droplet-based single-cell platforms to profile chromatin landscapes in single cells (scCUT&Tag) from complex tissues and during the differentiation of human embryonic stem cells. We focused on profiling polycomb group (PcG) silenced regions marked by histone H3 Lys27 trimethylation (H3K27me3) in single cells as an orthogonal approach to chromatin accessibility for identifying cell states. We show that scCUT&Tag profiling of H3K27me3 distinguishes cell types in human blood and allows the generation of cell-type-specific PcG landscapes from heterogeneous tissues. Furthermore, we used scCUT&Tag to profile H3K27me3 in a patient with a brain tumor before and after treatment, identifying cell types in the tumor microenvironment and heterogeneity in PcG activity in the primary sample and after treatment.
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