Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer
Cite
Li, R., Ferdinand, J.R., Loudon, K.W., Bowyer, G.S., Laidlaw, S., Muyas, F., Mamanova, L., Neves, J.B., Bolt, L., Fasouli, E.S. and Lawson, A.R., 2022. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer cell, 40(12), pp.1583-1599.
https://doi.org/10.1016/j.ccell.2022.11.001
Abstract
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8+ T cell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target.
Datasets
1. Single-cell transcriptomic datasets of Renal cell carcinoma patients
ExploreSample ID
Sampled site condition
Cell type
Region
Cell type (broad)
Subject ID
Assay
Disease
Sex
Tissue
Age group
Sample preservation method
Leiden clustering
Reference genome
5739STDY926697117,786 cells 5739STDY835121412,656 cells 5739STDY795880610,169 cells 5739STDY83512229,821 cells 5739STDY79588059,667 cells 5739STDY79588099,403 cells 5739STDY83512249,201 cells 5739STDY83512317,629 cells 5739STDY83512347,059 cells 5739STDY92669886,989 cells 5739STDY92669996,427 cells 5739STDY79588086,224 cells 5739STDY83512185,786 cells 5739STDY83512265,273 cells 5739STDY83512495,123 cells 5739STDY83512255,091 cells 5739STDY83512504,977 cells 5739STDY83512574,780 cells 5739STDY83512414,661 cells 5739STDY79587914,657 cells 5739STDY83512664,618 cells 5739STDY83512654,616 cells 5739STDY79587904,556 cells 5739STDY92669734,400 cells 5739STDY83512744,395 cells 5739STDY92669824,213 cells 5739STDY92669693,961 cells 5739STDY79588043,796 cells 5739STDY92669683,781 cells 5739STDY79587923,548 cells 5739STDY92669943,540 cells 5739STDY83512823,405 cells 5739STDY92669703,347 cells 5739STDY83512163,244 cells 5739STDY92669933,236 cells 5739STDY92669853,088 cells 5739STDY79587933,019 cells 5739STDY83512132,957 cells 5739STDY83512172,954 cells 5739STDY92669802,948 cells 5739STDY92669792,895 cells 5739STDY83512562,887 cells 5739STDY83512322,814 cells 5739STDY92669782,697 cells 5739STDY92669952,453 cells 5739STDY83512402,442 cells 5739STDY92669772,351 cells 5739STDY92669922,345 cells 5739STDY92669752,265 cells 5739STDY83512421,910 cells 5739STDY83512331,825 cells 5739STDY92669761,719 cells 5739STDY92669971,597 cells 5739STDY83512581,586 cells 5739STDY83512731,508 cells 5739STDY92669901,488 cells 5739STDY79588071,470 cells 5739STDY83512481,322 cells 5739STDY79588111,182 cells Tumour-normal23,482 cells Normal kidney11,838 cells Normal adrenal6,642 cells CD8+T_preEX-CXCR413,925 cells CD4+T_Naïve/CM10,360 cells CD4+T_Act-CXCR49,407 cells CD8+T_EX-CCL4L29,044 cells Classical Mono.48,368 cells NK-CX3CR1-high8,293 cells CD4+T_Act-NR4A15,713 cells CD8+T_Cycling-G2/M5,448 cells Activated KRT+ NK5,205 cells Classical Mono.24,020 cells Classical Mono.33,734 cells Non-classical Mono3,725 cells CD8+T_Naïve/CM2,506 cells CD4+T_Act-CCL52,500 cells CD8+T_RM-CXCL132,449 cells CD8+T_Cycling-G1/S1,722 cells CD8+T_Act-XCL1/21,603 cells Non-switched-memory_B1,396 cells Classical Mono.11,252 cells CD8+T_preEX-PMCH1,208 cells Activated_B-AREG1,129 cells Activated_B-RHOB888 cells Switched-memory_B669 cells CD4+T_Naïve/CM-patient-specific.1575 cells Type A intercalated cell383 cells CD principal cell370 cells CD4+T_INF-response258 cells CD4+T_Naïve/CM-patient-specific.2115 cells Connecting tubule cell107 cells Type B intercalated cell52 cells Pelvic urothelial cell48 cells 10x 5' transcription profiling270,855 cells nonpapillary renal cell carcinoma177,503 cells kidney oncocytoma12,610 cells kidney benign neoplasm57 cells adrenal tissue11,299 cells 
2. 10X Visium spatial transcriptomics on tumor-normal interface and tumor core tissue sections
ExploreSample ID
Subject ID
Region
Cell type
Assay
Disease
Sex
Tissue
Age group
Reference genome
Leiden clustering
6800STDY124994083,935 cells 6800STDY124994063,352 cells 6800STDY124994103,008 cells 6800STDY124995082,831 cells 6800STDY124995092,811 cells 6800STDY124995022,700 cells 6800STDY124995042,670 cells 6800STDY124995032,661 cells 6800STDY124995052,580 cells 6800STDY124995072,145 cells 6800STDY124994132,102 cells 6800STDY124994092,085 cells 6800STDY124994112,048 cells 6800STDY124995062,029 cells 6800STDY124994121,047 cells 6800STDY12499407832 cells naive thymus-derived CD4-positive, alpha-beta T cell10,165 cells epithelial cell of proximal tubule segment 15,309 cells collagen secreting cell3,424 cells kidney loop of Henle ascending limb epithelial cell2,510 cells epithelial cell of proximal tubule850 cells kidney collecting duct principal cell354 cells endothelial cell256 cells kidney loop of Henle thick ascending limb epithelial cell226 cells natural killer cell178 cells MHC-II-positive classical monocyte113 cells classical monocyte98 cells kidney connecting tubule principal cell57 cells CD8-positive, alpha-beta T cell48 cells epithelial cell of proximal tubule segment 339 cells kidney distal convoluted tubule epithelial cell37 cells endothelial cell of lymphatic vessel23 cells renal alpha-intercalated cell17 cells conventional dendritic cell11 cells CD4-positive, alpha-beta T cell4 cells activated type II NK T cell4 cells kidney pelvis urothelial cell3 cells renal beta-intercalated cell2 cells non-classical monocyte1 cells CD4-positive, CD25-positive, alpha-beta regulatory T cell1 cells Visium Spatial Gene Expression V138,836 cells nonpapillary renal cell carcinoma38,836 cells 
Alias names
EGAD00001008030, EGAD00001008781