DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction
Name
nihms-1531916.pdf
Description
Accepted version
Size
2.29 MB
Format
Unknown
Checksum (MD5)
e390c4ffcbb7bc473463e4e8f6f8baec
Author(s)
Weinstein, Joshua A.
Regev, Aviv
Zhang, Feng
Date Issued
June 2019
Journal
Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
Analyzing the spatial organization of molecules in cells and tissues is a cornerstone of biological research and clinical practice. However, despite enormous progress in molecular profiling of cellular constituents, spatially mapping them remains a disjointed and specialized machinery-intensive process, relying on either light microscopy or direct physical registration. Here, we demonstrate DNA microscopy, a distinct 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 with precise sequence information. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system. DNA microscopy is an optics-free imaging method based on chemical reactions and a computational algorithm to infer spatial organization of transcripts while simultaneously preserving full sequence information.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Howard Hughes Medical Institute
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2019.05.019
