Single-cell intracellular epitope and transcript detection reveals signal transduction dynamics

Cell Rep Methods. 2021 Sep 15;1(5):100070. doi: 10.1016/j.crmeth.2021.100070. eCollection 2021 Sep 27.

Abstract

To further our understanding of how biochemical information flows through cells upon external stimulation, we require single-cell multi-omics methods that concurrently map changes in (phospho)protein levels across signaling networks and the associated gene expression profiles. Here, we present quantification of RNA and intracellular epitopes by sequencing (QuRIE-seq), a droplet-based platform for single-cell RNA and intra- and extracellular (phospho)protein quantification through sequencing. We applied QuRIE-seq to quantify cell-state changes at both the signaling and the transcriptome level after 2-, 4-, 6-, 60-, and 180-min stimulation of the B cell receptor pathway in Burkitt lymphoma cells. Using the multi-omics factor analysis (MOFA+) framework, we delineated changes in single-cell (phospho)protein and gene expression patterns over multiple timescales and revealed the effect of an inhibitory drug (ibrutinib) on signaling and gene expression landscapes.

Keywords: BJAB; droplet microfluidics; gene expression; high throughput; ibrutinib; multi-omics; proteome; signaling networks; single cell; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Proteins
  • RNA*
  • Signal Transduction / genetics
  • Transcriptome*

Substances

  • RNA
  • Proteins