生物
转录因子
DNA结合位点
计算生物学
基因表达
结合位点
细胞
遗传学
基因
发起人
作者
Arnav Moudgil,Michael Wilkinson,Xuhua Chen,June He,Alexander J. Cammack,Michael J. Vasek,Tomás Lagunas,Zongtai Qi,Matthew A. Lalli,Chuner Guo,Samantha A. Morris,Robi D. Mitra
出处
期刊:Cell
[Elsevier]
日期:2020-08-01
卷期号:182 (4): 992-1008.e21
被引量:58
标识
DOI:10.1016/j.cell.2020.06.037
摘要
Cellular heterogeneity confounds in situ assays of transcription factor (TF) binding. Single-cell RNA sequencing (scRNA-seq) deconvolves cell types from gene expression, but no technology links cell identity to TF binding sites (TFBS) in those cell types. We present self-reporting transposons (SRTs) and use them in single-cell calling cards (scCC), a novel assay for simultaneously measuring gene expression and mapping TFBS in single cells. The genomic locations of SRTs are recovered from mRNA, and SRTs deposited by exogenous, TF-transposase fusions can be used to map TFBS. We then present scCC, which map SRTs from scRNA-seq libraries, simultaneously identifying cell types and TFBS in those same cells. We benchmark multiple TFs with this technique. Next, we use scCC to discover BRD4-mediated cell-state transitions in K562 cells. Finally, we map BRD4 binding sites in the mouse cortex at single-cell resolution, establishing a new method for studying TF biology in situ.
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