Single-cell transcriptome analysis reveals reciprocal epithelial and endothelial cell evolution in ovarian cancer
Langchao Liang,
Chaochao Chai,
Anmin Liu,
Aisha Shigna Nadukkandy,
Sowmiya Kalaiselvan,
Camilla Blunk Brandt,
Wandong Zhao,
Hanbo Li,
Lin Lin,
Jianmin Wu,
Yonglun Luo
Affiliations
Langchao Liang
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Science, BGI-Research, Qingdao 266555, China
Chaochao Chai
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Science, BGI-Research, Qingdao 266555, China
Anmin Liu
HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
Aisha Shigna Nadukkandy
Department of Biomedicine, Aarhus University, Aarhus, Denmark
Sowmiya Kalaiselvan
Department of Biomedicine, Aarhus University, Aarhus, Denmark
Camilla Blunk Brandt
Department of Biomedicine, Aarhus University, Aarhus, Denmark
Wandong Zhao
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Science, BGI-Research, Qingdao 266555, China
Hanbo Li
Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Science, BGI-Research, Qingdao 266555, China
Lin Lin
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
Jianmin Wu
HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China; Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China; Corresponding author
Yonglun Luo
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Corresponding author
Summary: Tumor neovascularization mediated by endothelial cells (ECs) is essential for ovarian cancer (OC) progression, but interactions between epithelial cells and ECs are not well understood. Here, we analyze single-cell transcriptome of 87,847 epithelial cells and 11,696 ECs from fallopian tubes, primary and metastatic ovarian tumors. Cell differentiation trajectory analysis reveals that fallopian tube cells exhibit a potential development trend toward primary OC epithelial cells. We identify a sub-population of fallopian tube epithelial cells (FTSEC3), which highly express tumor cell markers and are enriched in vascular endothelial growth factor production. Two neovascularization-related EC phenotypes (MKI67+ proliferating ECs and ESM1+ tip cells) are specially found in ovarium tumors, which exhibit strong interactions with FTSEC3. We validate that genetic disruption of LAMININ and TGF-β with CRISPR in ECs inhibits sprouting angiogenesis. In summary, this study reveals a reciprocal evolution and interaction between epithelial and ECs in OC development and progression.
