Simultaneous profiling of chromatin architecture and transcription in single cells
Simultaneous profiling of chromatin architecture and transcription in single cells
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DOI：
10.1038/s41594-023-01066-9
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发表时间：
2023-08
影响因子：
16.8
通讯作者：
Jiale Qu;Junyi Sun;Cai Zhao;Xinyi Liu;Xinyao Zhang;Shaoshuai Jiang;Chao Wei;Hao-Peng Yu;Xiaoxi Zeng;Lili Fan;Junjun Ding
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文献类型：
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作者：
Jiale Qu;Junyi Sun;Cai Zhao;Xinyi Liu;Xinyao Zhang;Shaoshuai Jiang;Chao Wei;Hao-Peng Yu;Xiaoxi Zeng;Lili Fan;Junjun Ding
染色质的三维结构在发育和疾病中起着至关重要的作用，这两者都与转录变化有关。然而，由于单细胞染色质结构和转录的异质性，三维染色质结构和基因表达之间的调控关系很难解释的基础上散装细胞群体。在这里，我们开发了一种单细胞，多模式，组学方法，允许通过测序（单细胞转录组测序（scCARE-seq））同时检测染色质结构和信使RNA表达。应用scCARE-seq检查从2 i到血清的单个小鼠胚胎干细胞的染色质结构和转录，我们观察到与单细胞染色质构象捕获相比，细胞簇的分离得到改善。此外，在通过scCARE-seq提取的染色质结构定义每个细胞的细胞周期阶段后，我们发现染色质结构的周期性变化与细胞周期中的转录平行发生。这些发现强调了scCARE-seq促进全面分析的潜力，这可能会促进我们对同一个单细胞中染色质结构和转录的理解。
The three-dimensional structure of chromatin plays a crucial role in development and disease, both of which are associated with transcriptional changes. However, given the heterogeneity in single-cell chromatin architecture and transcription, the regulatory relationship between the three-dimensional chromatin structure and gene expression is difficult to explain based on bulk cell populations. Here we develop a single-cell, multimodal, omics method allowing the simultaneous detection of chromatin architecture and messenger RNA expression by sequencing (single-cell transcriptome sequencing (scCARE-seq)). Applying scCARE-seq to examine chromatin architecture and transcription from 2i to serum single mouse embryonic stem cells, we observe improved separation of cell clusters compared with single-cell chromatin conformation capture. In addition, after defining the cell-cycle phase of each cell through chromatin architecture extracted by scCARE-seq, we find that periodic changes in chromatin architecture occur in parallel with transcription during the cell cycle. These findings highlight the potential of scCARE-seq to facilitate comprehensive analyses that may boost our understanding of chromatin architecture and transcription in the same single cell.