4.5 Article

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

Journal

GENOME BIOLOGY
Volume 21, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13059-020-01958-9

Keywords

Index sorting; Single-cell RNA sequencing; Microfluidics; Flow cytometry

Funding

  1. National Science Foundation [DBI-1253293]
  2. National Institutes of Health New Innovator Award [DP2AR068129, R01HG008978]
  3. National Science Foundation Technology Center grant [DBI-1548297]
  4. UCSF Center for Cellular Construction

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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.

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