Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH

Nature. 2019 Apr;568(7751):235-239. doi: 10.1038/s41586-019-1049-y. Epub 2019 Mar 25.


Imaging the transcriptome in situ with high accuracy has been a major challenge in single-cell biology, which is particularly hindered by the limits of optical resolution and the density of transcripts in single cells1-5. Here we demonstrate an evolution of sequential fluorescence in situ hybridization (seqFISH+). We show that seqFISH+ can image mRNAs for 10,000 genes in single cells-with high accuracy and sub-diffraction-limit resolution-in the cortex, subventricular zone and olfactory bulb of mouse brain, using a standard confocal microscope. The transcriptome-level profiling of seqFISH+ allows unbiased identification of cell classes and their spatial organization in tissues. In addition, seqFISH+ reveals subcellular mRNA localization patterns in cells and ligand-receptor pairs across neighbouring cells. This technology demonstrates the ability to generate spatial cell atlases and to perform discovery-driven studies of biological processes in situ.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Brain / anatomy & histology*
  • Brain / cytology
  • Brain / metabolism*
  • Dopaminergic Neurons / metabolism
  • Endothelial Cells / metabolism
  • Female
  • Gene Expression Profiling
  • In Situ Hybridization, Fluorescence / methods*
  • Ligands
  • Male
  • Mice
  • Microglia / metabolism
  • Organ Specificity
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics*
  • Single-Cell Analysis / methods*
  • Transcriptome / genetics*


  • Ligands
  • RNA, Messenger