Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma

Abstract

Single cell dissociation antibody staining and FACS sorting Cellular atlas DEGs Cellular interaction Ligand Recepto r Immunostaining Functional assays Correlation analysis Droplet-based scRNA-seq Data Cell 1 Cell 2 Cell x Gene 1 Gene 2 Gene y Highlights Single cell transcriptomic datasets are a valuable resource to dissect cellular diversity and intercellular crosstalk of human ICCs. Malignant cells displayed remarkable inter-tumor heterogeneity and Tregs revealed highly immunosuppressive characteristics. Six distinct fibroblast subsets were defined in ICCs and adjacent tissues. CD146 + vCAFs, comprising most of the fibroblasts, had tight interactions with malignant cells through IL-6/IL-6R axis. Tumor exosomal miR-9-5p elicited IL-6 expression in vCAFs, contributing to ICC progression via upregulation of EZH2.

Deciphering cell–cell interactions and communication from gene expression

“…Tumours and their surrounding microenvironments are complex communities of cells that modify local immune cell functions. Studying CCC within these communities can reveal how cells communicate in these ecosystems 54 , 59 – 64 and help guide the development of effective cancer immunotherapies just as the inhibition of CCC through PD1 and PDL1 has revolutionized the field 65 , 66 . CCC analyses have also elucidated crosstalk between tumour and stroma 67 , 68 and communication pathways used by tumours 69 – 71 .…”

Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: A prospective cohort study

“…In fact, a series of chromosomal aberrations have been revealed among BTC patients [42] , [43] , [44] . A recent single-cell RNA sequencing analysis on cholangiocarcinoma has employed the CNV signals to identify the tumor cell cluster [45] .…”

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

“…Besides the direct impact on tumor cells by regulating their proliferation, survival and migration, CAFs regulate angiogenesis and immunity by secreting a vast number of soluble chemokines and growth factors, such as chemokine (C-X-C motif) ligand 14 (CXCL14), interleukin 8 (IL-8), IL-13, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF), that stimulate stromal cells and recruit inflammatory immune cells in tumor bed [26]. Recently, a study by Zhang et al evaluated both iCCA and peritumoral samples to elucidate the comprehensive transcriptomic landscape and the intercellular communication network [28]. They identified six distinct fibroblast subsets, with a prevalent population of CD146 + vascular CAFs that highly express microvasculature signature genes and high levels of immunosuppressive IL-6.…”