RT Journal Article
SR Electronic
T1 Micro-region transcriptomics of fixed human tissue using Pick-Seq
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.18.431004
DO 10.1101/2021.03.18.431004
A1 Maliga, Zoltan
A1 Nirmal, Ajit J.
A1 Ericson, Nolan G.
A1 Boswell, Sarah A.
A1 U’Ren, Lance
A1 Podyminogin, Rebecca
A1 Chow, Jennifer
A1 Chen, Yu-An
A1 Chen, Alyce A.
A1 Weinstock, David M.
A1 Lian, Christine G.
A1 Murphy, George F.
A1 Kaldjian, Eric P.
A1 Santagata, Sandro
A1 Sorger, Peter K.
YR 2021
UL http://biorxiv.org/content/early/2021/03/19/2021.03.18.431004.abstract
AB 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.Competing Interest StatementNE, LU, RP, JC, and EJK are or have been employees of RareCyte Inc. PKS is a member of the SAB or BOD of Applied BioMath, RareCyte Inc., and Glencoe Software, which distributes a commercial version of the OMERO database; PKS is also a member of the NanoString SAB. SS is a consultant for RareCyte Inc. All other authors declare they have no competing interests.