Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing [article]

Ansam Sinjab, Guangchun Han, Kieko Kobayashi, Warapen Treekitkarnmongkol, Patrick Brennan, Minghao Dang, Dapeng Hao, Ruiping Wang, Enyu Dai, Hitoshi Dejima, Jiexin Zhang, Elena Bogatenkova (+30 others)
2020 bioRxiv   pre-print
Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and fourteen multi-region normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to the LUADs. LUADs exhibit pronounced intratumor cell heterogeneity within single
more » ... within single sites and transcriptional lineage-plasticity programs driven by KRAS mutations. T regulatory cell phenotypes are increased in normal tissues with closer proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages and inflammatory dendritic cells. Further, the LUAD ecosystem harbors gain of ligand-receptor based interactions involving increased expression of CD24 antigen on epithelial cells and SIGLEC10 on myeloid subsets. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for treatment.
doi:10.1101/2020.09.04.283739 fatcat:dprno6dnnfdrvfsc4yopwyrjxe