RT Journal Article
SR Electronic
T1 Spatial epitope barcoding reveals subclonal tumor patch behaviors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.29.449991
DO 10.1101/2021.06.29.449991
A1 Xavier Rovira-Clavé
A1 Alexandros P. Drainas
A1 Sizun Jiang
A1 Yunhao Bai
A1 Maya Baron
A1 Bokai Zhu
A1 Maxim Markovic
A1 Garry L. Coles
A1 Michael C. Bassik
A1 Julien Sage
A1 Garry P. Nolan
YR 2021
UL http://biorxiv.org/content/early/2021/06/30/2021.06.29.449991.abstract
AB Intratumoral variability is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are unsuitable to accurately track phenotypes and subclonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitope combinatorial tags (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using this platform, we dissected the spatial component of cell lineages and phenotypes in a xenograft model of small-cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of subclonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in this model. In tumors harboring a fraction of PTEN-deficient cancer cells, we uncovered a non-autonomous increase of subclonal patch size in PTEN wildtype cancer cells. EpicMIBI can facilitate in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.Competing Interest StatementJ.S. receives research funding from Pfizer. G.P.N. is co-founder and stockholder of Ionpath, Inc. and inventor on patent US 2019/0162729. The other authors declare no competing interests.