| Evidence |
Endothelial cellss, tissue-specificity confined to normal tissue Clustering the transcriptomes of 8223 Endothelial cellss (ECs) using unaligned and CCA-aligned approaches identified, respectively, 13 and 9 clusters, each with corresponding marker genes (Fig. 2a_c; Supplementary information, Fig. S2a_c). Five CCA-aligned clusters were shared between cancer types (Fig. 2d, e), including, based on marker gene expression, C1_ESM1 tip cells (ESM1, NID2), C2_ACKR1 high endothelial venules (HEVs) and venous ECs (ACKR1, SELP), C3_CA4 capillary (CA4, CD36), C4_FBLN5 arterial (FBLN5, GJA5) and C5_PROX1 lymphatic (PROX1, PDPN) ECs. Three other clusters displayed T-cell (C6_CD3D), pericyte (C7_RGS5) and myeloid-specific (C8_AIF1) marker genes and consisted of doublet cells, while one cluster consisted of low-quality ECs (C9; Supplementary information, Fig. S2d, e). Tip ECs only resided in malignant tissue and were most prevalent in CRC, while also HEVs were enriched in tumors. In contrast, capillary ECs (cECs) were enriched in normal tissue (Fig. 2d_f; Supplementary information, Fig. S2f). We identified several genes differentially expressed between tumor and normal tissue (Supplementary information, Fig. S2g and Table S7). For instance, the pro-angiogenic factor perlecan (or HSPG2) was highly expressed in tumor versus normal cECs. |
