当前位置: X-MOL 学术Science › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Joint profiling of chromatin accessibility and gene expression in thousands of single cells
Science ( IF 56.9 ) Pub Date : 2018-08-30 , DOI: 10.1126/science.aau0730
Junyue Cao 1, 2 , Darren A. Cusanovich 1 , Vijay Ramani 1 , Delasa Aghamirzaie 1 , Hannah A. Pliner 1 , Andrew J. Hill 1 , Riza M. Daza 1 , Jose L. McFaline-Figueroa 1 , Jonathan S. Packer 1 , Lena Christiansen 3 , Frank J. Steemers 3 , Andrew C. Adey 4, 5 , Cole Trapnell 1, 6, 7 , Jay Shendure 1, 6, 7, 8
Affiliation  

Single-cell chromatin and RNA analysis Single-cell analyses have begun to provide insight into the differences among and within the individual cells that make up a tissue or organism. However, technological barriers owing to the small amount of material present in each single cell have prevented parallel analyses. Cao et al. present sci-CAR, a pooled barcode method that jointly analyzes both the RNA transcripts and chromatin profiles of single cells. By applying sci-CAR to lung adenocarcinoma cells and mouse kidney tissue, the authors demonstrate precision in assessing expression and genome accessibility at a genome-wide scale. The approach provides an improvement over bulk analysis, which can be confounded by differing cellular subgroups. Science, this issue p. 1380 A technique termed sci-CAR can assess both chromatin accessibility and RNA transcription at the single-cell level. Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing–based coassay that jointly profiles chromatin accessibility and mRNA (CAR) in each of thousands of single cells. As a proof of concept, we apply sci-CAR to 4825 cells, including a time series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.

中文翻译:

数千个单细胞染色质可及性和基因表达的联合分析

单细胞染色质和 RNA 分析 单细胞分析已经开始提供对构成组织或生物体的单个细胞之间和内部差异的洞察。然而,由于每个单细胞中存在的材料量很少,技术障碍阻止了平行分析。曹等人。目前 sci-CAR,一种汇集条形码方法,可联合分析单细胞的 RNA 转录物和染色质图谱。通过将 sci-CAR 应用于肺腺癌细胞和小鼠肾组织,作者证明了在全基因组范围内评估表达和基因组可及性的精确性。该方法提供了对批量分析的改进,批量分析可能会被不同的细胞亚群混淆。科学,这个问题 p。1380 一种称为 sci-CAR 的技术可以在单细胞水平上评估染色质可及性和 RNA 转录。尽管我们可以越来越多地以单细胞分辨率测量转录、染色质、甲基化和分子生物学的其他方面,但大多数分析仅调查细胞生物学的一个方面。在这里,我们描述了 sci-CAR,这是一种基于组合索引的 coassay,它联合分析了数千个单细胞中每个细胞的染色质可及性和 mRNA (CAR)。作为概念证明,我们将 sci-CAR 应用于 4825 个细胞,包括地塞米松处理的时间序列,以及来自成年小鼠肾脏的 11,296 个细胞。利用所得数据,我们比较染色质可及性和基因表达的假时间动态,重建由 RNA 谱定义的细胞类型的染色质可及性谱,
更新日期:2018-08-30
down
wechat
bug