@article{Zimmerman01102022,
author = {Zimmerman, Stephanie M. and Fropf, Robin and Kulasekara, Bridget R. and Griswold, Maddy and Appelbe, Oliver and Bahrami, Arya and Boykin, Rich and Buhr, Derek L. and Fuhrman, Kit and Hoang, Margaret L. and Huynh, Quoc and Isgur, Lesley and Klock, Andrew and Kutchma, Alecksandr and Lasley, Alexa E. and Liang, Yan and McKay-Fleisch, Jill and Nelson, Jeffrey S. and Nguyen, Karen and Piazza, Erin and Rininger, Aric and Zollinger, Daniel R. and Rhodes, Michael and Beechem, Joseph M.}, 
title = {Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling},
volume = {32}, 
number = {10}, 
pages = {1892-1905}, 
year = {2022}, 
doi = {10.1101/gr.276206.121}, 
abstract ={Emerging spatial profiling technology has enabled high-plex molecular profiling in biological tissues, preserving the spatial and morphological context of gene expression. Here, we describe expanding the chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed in situ hybridization probes targeting the protein-coding genes of the human and mouse transcriptomes, referred to as the human or mouse Whole Transcriptome Atlas (WTA). Human and mouse WTAs were validated in cell lines for concordance with orthogonal gene expression profiling methods in regions ranging from ∼10–500 cells. By benchmarking against bulk RNA-seq and fluorescence in situ hybridization, we show robust transcript detection down to ∼100 transcripts per region. To assess the performance of WTA across tissue and sample types, we applied WTA to biological questions in cancer, molecular pathology, and developmental biology. Spatial profiling with WTA detected expected gene expression differences between tumor and tumor microenvironment, identified disease-specific gene expression heterogeneity in histological structures of the human kidney, and comprehensively mapped transcriptional programs in anatomical substructures of nine organs in the developing mouse embryo. Digital Spatial Profiling technology with the WTA assays provides a flexible method for spatial whole transcriptome profiling applicable to diverse tissue types and biological contexts.}, 
URL = {http://genome.cshlp.org/content/32/10/1892.abstract}, 
eprint = {http://genome.cshlp.org/content/32/10/1892.full.pdf+html}, 
journal = {Genome Research} 
}