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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Jul 26

PMID 32710817

Citations 40

Authors

Arnav Moudgil

Michael N Wilkinson

Xuhua Chen

June He

Alexander J Cammack

Michael J Vasek

Tomas Lagunas Jr

Zongtai Qi

Matthew A Lalli

Chuner Guo

Samantha A Morris

Joseph D Dougherty

Robi D Mitra

Affiliations

Soon will be listed here.

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.

Citing Articles

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