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

Date: 
July 11, 2018
Place: 
HSW 1057

Abstract

Retrieving high-content gene-expression information while retaining 3D positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. Here we develop and apply a technology for 3D intact-tissue RNA sequencing, termed STARmap (Spatially-resolved Transcript Amplicon Readout Mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1,020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy and reproducibility. Moving to thick tissue blocks, we observed a molecularly-defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells), and discovered a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.

Presenter: 
Theodore Roth
Publication Date: 
June 21, 2018
Presentation Paper: 
Time: 
12:00pm
Paper Author: 
Wang X1, Allen WE1,2, Wright MA1,3, Sylwestrak EL1, Samusik N4, Vesuna S1, Evans K1, Liu C1, Ramakrishnan C1, Liu J5, Nolan GP6, Bava FA6, Deisseroth K7,3,8.
Institution: 
1 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
2 Neuroscience Program, Stanford University, CA 94305, USA.
3 Department of Psychiatry and Behavioral Sciences, Stanford University, CA 94305, USA.
4 Baxter Laboratory, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
5 Department of Chemical Engineering, Stanford University, CA 94305, USA.
6 Baxter Laboratory, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. [email protected] [email protected] [email protected]
7 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. [email protected] [email protected] [email protected]
8 Howard Hughes Medical Institute, Stanford University, CA 94305, USA.
Journal: 
Science. 2018 Jun 21. pii: eaat5691. doi: 10.1126/science.aat5691. [Epub ahead of print]