Linked optical and gene expression profiling of single cells at high-throughput

Genome Biol. 2020 Feb 24;21(1):49. doi: 10.1186/s13059-020-01958-9.


Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analysis has provided insight into the molecular basis of cellular function, but current approaches have limited throughput. Here, we present a high-throughput platform for linked optical and gene expression profiling of single cells. We demonstrate accurate fluorescence and gene expression measurements on thousands of cells in a single experiment. We use the platform to characterize DNA and RNA changes through the cell cycle and correlate antibody fluorescence with gene expression. The platform's ability to isolate rare cell subsets and perform multiple measurements, including fluorescence and sequencing-based analysis, holds potential for scalable multi-modal single-cell analysis.

Keywords: Flow cytometry; Index sorting; Microfluidics; Single-cell RNA sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cells, Cultured
  • Flow Cytometry / methods
  • Gene Expression Profiling / methods*
  • HEK293 Cells
  • Humans
  • Mice
  • Microfluidics / methods
  • Nanopore Sequencing / methods
  • RNA-Seq / methods*
  • Single-Cell Analysis / methods*