An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome

Nat Struct Mol Biol. 2019 Nov;26(11):1063-1070. doi: 10.1038/s41594-019-0323-x. Epub 2019 Nov 6.


Simultaneous profiling of transcriptome and chromatin accessibility within single cells is a powerful approach to dissect gene regulatory programs in complex tissues. However, current tools are limited by modest throughput. We now describe an ultra high-throughput method, Paired-seq, for parallel analysis of transcriptome and accessible chromatin in millions of single cells. We demonstrate the utility of Paired-seq for analyzing the dynamic and cell-type-specific gene regulatory programs in complex tissues by applying it to mouse adult cerebral cortex and fetal forebrain. The joint profiles of a large number of single cells allowed us to deconvolute the transcriptome and open chromatin landscapes in the major cell types within these brain tissues, infer putative target genes of candidate enhancers, and reconstruct the trajectory of cellular lineages within the developing forebrain.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology*
  • Brain / embryology
  • Brain / metabolism
  • Chromatin / genetics*
  • Gene Expression Profiling / economics
  • Gene Expression Profiling / methods*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Single-Cell Analysis / economics
  • Single-Cell Analysis / methods*
  • Transcriptome*


  • Chromatin