RT Journal Article
SR Electronic
T1 DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 471219
DO 10.1101/471219
A1 Joshua A. Weinstein
A1 Aviv Regev
A1 Feng Zhang
YR 2018
UL http://biorxiv.org/content/early/2018/11/19/471219.abstract
AB Analyzing the spatial organization of molecules in cells and tissues is a cornerstone of biological research and clinical practice. However, despite enormous progress in profiling the molecular constituents of cells, spatially mapping these constituents remains a disjointed and machinery-intensive process, relying on either light microscopy or direct physical registration and capture. Here, we demonstrate DNA microscopy, a new imaging modality for scalable, optics-free mapping of relative biomolecule positions. In DNA microscopy of transcripts, transcript molecules are tagged in situ with randomized nucleotides, labeling each molecule uniquely. A second in situ reaction then amplifies the tagged molecules, concatenates the resulting copies, and adds new randomized nucleotides to uniquely label each concatenation event. An algorithm decodes molecular proximities from these concatenated sequences, and infers physical images of the original transcripts at cellular resolution. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system.