TY  - JOUR
A1  - Zimmerman, Stephanie M.
A1  - Fropf, Robin
A1  - Kulasekara, Bridget R.
A1  - Griswold, Maddy
A1  - Appelbe, Oliver
A1  - Bahrami, Arya
A1  - Boykin, Rich
A1  - Buhr, Derek L.
A1  - Fuhrman, Kit
A1  - Hoang, Margaret L.
A1  - Huynh, Quoc
A1  - Isgur, Lesley
A1  - Klock, Andrew
A1  - Kutchma, Alecksandr
A1  - Lasley, Alexa E.
A1  - Liang, Yan
A1  - McKay-Fleisch, Jill
A1  - Nelson, Jeffrey S.
A1  - Nguyen, Karen
A1  - Piazza, Erin
A1  - Rininger, Aric
A1  - Zollinger, Daniel R.
A1  - Rhodes, Michael
A1  - Beechem, Joseph M.
T1  - Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling
Y1  - 2022/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1892 
EP  - 1905 
DO  - 10.1101/gr.276206.121 
VL  - 32 
IS  - 10 
UR  - http://genome.cshlp.org/content/32/10/1892.abstract 
N2  - 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. 
ER  -