近日，美国圣路易斯华盛顿大学医学院Robi D. Mitra及其团队开发出自我报告转座子技术，可同时读取单个细胞的基因表达和转录因子结合。2020年7月24日，《细胞》在线发表了这一成果。

研究人员开发了自我报告转座子（SRT）技术，并将其用于单细胞calling cards（scCC），后者是一种用于同时测量基因表达和在单细胞中定位转录因子结合位点（TFBS）的新型检测方法。SRT的基因组位置可从mRNA中获取，并且通过外源TF-转座酶融合沉积的SRT可用于绘制TFBS图谱。然后，研究人员介绍了scCC，它可以从scRNA-seq库中映射SRT，并同时识别那些相同细胞中的细胞类型和TFBS。研究人员使用此技术对多个TF进行了基准测试。

接下来，研究人员使用scCC发现K562细胞中BRD4介导的细胞状态转变。最后，研究人员在小鼠皮层中以单细胞分辨率绘制了BRD4结合位点的图谱，从而建立了一种原位研究TF生物学的新方法。

据悉，细胞异质性混淆了转录因子（TF）结合的原位测定。单细胞RNA测序（scRNA-seq）可将细胞类型从基因表达中解卷积，但是没有任何技术将细胞身份与那些细胞类型中的TF结合位点（TFBS）联系起来。

附：英文原文

Title: Self-Reporting Transposons Enable Simultaneous Readout of Gene Expression and Transcription Factor Binding in Single Cells

Author: Arnav Moudgil, Michael N. Wilkinson, Xuhua Chen, June He, Alexander J. Cammack, Michael J. Vasek, Tomás Lagunas, Zongtai Qi, Matthew A. Lalli, Chuner Guo, Samantha A. Morris, Joseph D. Dougherty, Robi D. Mitra

Issue&Volume: 2020-07-24

Abstract: 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.

DOI: 10.1016/j.cell.2020.06.037

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30814-X