小柯机器人

研究揭示细胞转录组与染色质可及性图谱
2019-10-15 12:31

美国加州大学圣地亚哥分校Kun Zhang小组利用高通量测序方法,揭示了同一细胞中转录组和染色质可及性图谱。 这一研究成果2019年10月14日在线发表在《自然—生物技术》上。

研究人员利用基于液滴的单核染色质可及性和mRNA表达测序(SNARE-seq)的手段进行大规模测序,这种方法可以将细胞的转录组与其可利用的染色质连接起来。具体而言,在许多平行液滴中,Tn5转座酶在通透性细胞核中捕获了可及的位点,利于同一细胞中mRNA分子和DNA条形码的标记。

为了证明SNARE-seq的实用性,研究者构建了新生和成年小鼠大脑皮层5081和10309个细胞的连接概况。研究人员重建了主要和稀有细胞类型的转录组和表观遗传图谱,揭示了对于低丰度细胞来说谱系特异性的可及位点,并在神经发育过程中将启动子可及性与转录水平联系起来。

据悉,单细胞RNA测序可以揭示细胞的转录状态,但对于开放或可进入染色质区域相关的上游调节环境知之甚少。相同细胞内可及染色质和RNA的联合分析将使转录调控与其输出相匹配。

附:英文原文

Title: High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell

Author: Song Chen, Blue B. Lake, Kun Zhang

Issue&Volume: 2019-10-14

Abstract: 

Single-cell RNA sequencing can reveal the transcriptional state of cells, yet provides little insight into the upstream regulatory landscape associated with open or accessible chromatin regions. Joint profiling of accessible chromatin and RNA within the same cells would permit direct matching of transcriptional regulation to its outputs. Here, we describe droplet-based single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq), a method that can link a cell’s transcriptome with its accessible chromatin for sequencing at scale. Specifically, accessible sites are captured by Tn5 transposase in permeabilized nuclei to permit, within many droplets in parallel, DNA barcode tagging together with the mRNA molecules from the same cells. To demonstrate the utility of SNARE-seq, we generated joint profiles of 5,081 and 10,309 cells from neonatal and adult mouse cerebral cortices, respectively. We reconstructed the transcriptome and epigenetic landscapes of major and rare cell types, uncovered lineage-specific accessible sites, especially for low-abundance cells, and connected the dynamics of promoter accessibility with transcription level during neurogenesis.

DOI: 10.1038/s41587-019-0290-0

Source: https://www.nature.com/articles/s41587-019-0290-0

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


本期文章:《自然—生物技术》:Online/在线发表

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