研究揭示細胞轉錄組與染色質可及性圖譜

研究揭示細胞轉錄組與染色質可及性圖譜

作者：

小柯機器人

發布時間：2019/10/15 12:31:02

美國加州大學聖地牙哥分校Kun Zhang小組利用高通量測序方法，揭示了同一細胞中轉錄組和染色質可及性圖譜。 這一研究成果2019年10月14日在線發表在《自然—生物技術》上。

研究人員利用基於液滴的單核染色質可及性和mRNA表達測序（SNARE-seq）的手段進行大規模測序，這種方法可以將細胞的轉錄組與其可利用的染色質連接起來。具體而言，在許多平行液滴中，Tn5轉座酶在通透性細胞核中捕獲了可及的位點，利於同一細胞中mRNA分子和DNA條形碼的標記。

為了證明SNARE-seq的實用性，研究者構建了新生和成年小鼠大腦皮層5081和10309個細胞的連接概況。研究人員重建了主要和稀有細胞類型的轉錄組和表觀遺傳圖譜，揭示了對於低豐度細胞來說譜系特異性的可及位點，並在神經發育過程中將啟動子可及性與轉錄水平聯繫起來。

據悉，單細胞RNA測序可以揭示細胞的轉錄狀態，但對於開放或可進入染色質區域相關的上遊調節環境知之甚少。相同細胞內可及染色質和RNA的聯合分析將使轉錄調控與其輸出相匹配。

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