An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome
An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome
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DOI：
10.1038/s41594-019-0323-x
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发表时间：
2019-11-01
影响因子：
16.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Zhu, Chenxu;Yu, Miao;Ren, Bing
单细胞内转录组和染色质可及性的同时分析是剖析复杂组织中基因调控程序的有力方法。然而，当前的工具受到适度吞吐量的限制。我们现在描述一种超高通量方法Paired-seq，用于在数百万个单细胞中并行分析转录组和可接近的染色质。我们展示了Paired-seq的实用性，通过将其应用于小鼠成年大脑皮层和胎儿前脑，分析复杂组织中的动态和细胞类型特异性基因调控程序。大量单细胞的联合概况使我们能够在这些脑组织内的主要细胞类型中解卷积转录组和开放染色质景观，推断候选增强子的推定靶基因，并重建发育中前脑内细胞谱系的轨迹。
Simultaneous profiling of transcriptome and chromatin accessibility within single cells is a powerful approach to dissect gene regulatory programs in complex tissues. However, current tools are limited by modest throughput. We now describe an ultra high-throughput method, Paired-seq, for parallel analysis of transcriptome and accessible chromatin in millions of single cells. We demonstrate the utility of Paired-seq for analyzing the dynamic and cell-type-specific gene regulatory programs in complex tissues by applying it to mouse adult cerebral cortex and fetal forebrain. The joint profiles of a large number of single cells allowed us to deconvolute the transcriptome and open chromatin landscapes in the major cell types within these brain tissues, infer putative target genes of candidate enhancers, and reconstruct the trajectory of cellular lineages within the developing forebrain.