Micro-region transcriptomics of fixed human tissue using Pick-Seq
Maliga, Z.; Nirmal, A. J.; Ericson, N. G.; Boswell, S. A.; U'Ren, L.; Podyminogin, R.; Chow, J.; Chen, Y.-A.; Chen, A. A.; Weinstock, D. M.; Lian, C. G.; Murphy, G. F.; Kaldjian, E. P.; Santagata, S.; Sorger, P. K.
Show abstract
Spatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology and disease. Recently developed spatial transcriptomic methods use fresh-frozen specimens but most diagnostic specimens, clinical trials, and tissue archives rely on formaldehyde-fixed tissue. Here we describe the Pick-Seq method for deep spatial transcriptional profiling of fixed tissue. Pick-Seq is a form of micro-region sequencing in which small regions of tissue, containing 5-20 cells, are mechanically isolated on a microscope and then sequenced. We demonstrate the use of Pick-Seq with several different fixed and frozen human specimens. Application of Pick-Seq to a human melanoma with complex histology reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immuno-editing. Parallel imaging confirms changes in immuno-phenotypes and cancer cell states. This work demonstrates the ability of Pick-Seq to generate deep spatial transcriptomic data from fixed and archival tissue with multiplexed imaging in parallel.
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