Single-cell RNA sequencing reveals cancer stem-like cells and dynamics in tumor microenvironment during cholangiocarcinoma progression

Author:

Golino, Jihye L

Bian, Jing

Wang, Xin

Fu, Jianyang

Zhu, Xiao Bin

Yeo, Julie

Kelly,Michael

Escorcia, Freddy E

Cam, Maggie

Xie, Changqing
Author Address

Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., CCR Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States., Molecular Imaging Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., NCI CCR Liver Cancer Program, Bethesda, MD, United States.,

Abstract:

Cholangiocarcinoma is a malignancy of the bile ducts that is driven by activities of cancer stem-like cells and characterized by a heterogeneous tumor microenvironment. To better understand the transcriptional profiles of cancer stem-like cells and dynamics in the tumor microenvironment during the progression of cholangiocarcinoma, we performed single-cell RNA analysis on cells collected from three different timepoints of tumorigenesis in a YAP/AKT mouse model. Bulk RNA sequencing data from TCGA (The Cancer Genome Atlas program) and ICGC cohorts were used to verify and support the finding. In vitro and in vivo experiments were performed to assess the stemness of cancer stem-like cells. We identified Tm4sf1high malignant cells as cancer stem-like cells. Across timepoints of cholangiocarcinoma formation in YAP/AKT mice, we found dynamic change in cancer stem-like cell/stromal/immune cell composition. Nevertheless, the dynamic interaction among cancer stem-like cells, immune cells, and stromal cells at different timepoints was elaborated. Collectively, these data serve as a useful resource for better understanding cancer stem-like cell and malignant cell heterogeneity, stromal cell remodeling, and immune cell reprogramming. It also sheds new light on transcriptomic dynamics during cholangiocarcinoma progression at single-cell resolution. Copyright © 2023 Golino, Bian, Wang, Fu, Zhu, Yeo, Kelly, Escorcia, Cam and Xie.

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