biostudies-literatureUnknown13(1)Song GIntrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCA^phl) and peripheral small duct type (iCCA^pps). S100P + SPP1- iCCA^phl has significantly reduced levels of infiltrating CD4⁺ T cells, CD56⁺ NK cells, and increased CCL18⁺ macrophages and PD1⁺CD8⁺ T cells compared to S100P-SPP1 + iCCA^pps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCA^pps has significantly more SPP1⁺ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCA^phl. Moreover, S100P-SPP1 + iCCA^pps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.Nature communications1642https://www.ebi.ac.uk/biostudies/studies/S-EPMC8960779biostudies-literatureSingle-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.PMC8960779Zhang JLin YJiang SZhang SCheng YShi YLiu YRao DFan JWang XWu YZhou JLi JXi RSong GGao QJi SHuang SCao YZhang XKe AMeng LMa JLin JJi YYang SfalseSingle-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCA^phl) and peripheral small duct type (iCCA^pps). S100P + SPP1- iCCA^phl has significantly reduced levels of infiltrating CD4⁺ T cells, CD56⁺ NK cells, and increased CCL18⁺ macrophages and PD1⁺CD8⁺ T cells compared to S100P-SPP1 + iCCA^pps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCA^pps has significantly more SPP1⁺ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCA^phl. Moreover, S100P-SPP1 + iCCA^pps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.2022-01-01T00:00:00Z2022 Mar2025-04-18T23:46:57.685Z2025-02-19T04:57:25.276ZS-EPMC89607793534713410.1038/s41467-022-29164-0