Gene

Illumina dye sequencing

Phenotype

Deep sequencing

Genome

Gene expression

Transcriptome

Exome sequencing

Neuroscience

Single cell sequencing

Brain tissue

DNA sequencing

Genetics

Computational biology

In situ hybridization

Biology

Science

Transcriptome mapping in the 3D brain RNA sequencing samples the entire transcriptome but lacks anatomical information. In situ hybridization, on the other hand, can only profile a small number of transcripts. In situ sequencing technologies address these shortcomings but face a challenge in dense, complex tissue environments. Wang et al. combined an efficient sequencing approach with hydrogel-tissue chemistry to develop a multidisciplinary technology for three-dimensional (3D) intact-tissue RNA sequencing (see the Perspective by Knöpfel). More than 1000 genes were simultaneously mapped in sections of mouse brain at single-cell resolution to define cell types and circuit states and to reveal cell organization principles. Science , this issue p. eaat5691 ; see also p. 328

Three-dimensional intact-tissue sequencing of single-cell transcriptional states