Open AccessZipSeq: barcoding for real-time mapping of single cell transcriptomes
Author(s) -
Kenneth H. Hu,
John P. Eichorst,
Christopher S. McGinnis,
David M. Patterson,
Eric D. Chow,
Kelly Kersten,
Stephen C. Jameson,
Zev J. Gartner,
Rao Av,
Matthew F. Krummel
Publication year - 2020
Publication title -
nature methods
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 19.469
H-Index - 318
eISSN - 1548-7105
pISSN - 1548-7091
DOI - 10.1038/s41592-020-0880-2
Subject(s) - transcriptome , multicellular organism , biology , computational biology , cell , phenotype , microbiology and biotechnology , gene expression profiling , gene , gene expression , genetics
Spatial transcriptomics seeks to integrate single cell transcriptomic data within the three-dimensional space of multicellular biology. Current methods to correlate a cell's position with its transcriptome in living tissues have various limitations. We developed an approach, called 'ZipSeq', that uses patterned illumination and photocaged oligonucleotides to serially print barcodes ('zipcodes') onto live cells in intact tissues, in real time and with an on-the-fly selection of patterns. Using ZipSeq, we mapped gene expression in three settings: in vitro wound healing, live lymph node sections and a live tumor microenvironment. In all cases, we discovered new gene expression patterns associated with histological structures. In the tumor microenvironment, this demonstrated a trajectory of myeloid and T cell differentiation from the periphery inward. A combinatorial variation of ZipSeq efficiently scales in the number of regions defined, providing a pathway for complete mapping of live tissues, subsequent to real-time imaging or perturbation.