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

doi:10.1016/j.isci.2024.111417

Single-cell transcriptome analysis reveals reciprocal epithelial and endothelial cell evolution in ovarian cancer

iScience. 2024 Nov 19;27(12):111417. doi: 10.1016/j.isci.2024.111417. eCollection 2024 Dec 20.

Authors

Langchao Liang^{1

2}, Chaochao Chai^{1

2}, Anmin Liu^{3

4}, Aisha Shigna Nadukkandy⁵, Sowmiya Kalaiselvan⁵, Camilla Blunk Brandt⁵, Wandong Zhao^{1

2}, Hanbo Li², Lin Lin^{5

6}, Jianmin Wu^{3

7}, Yonglun Luo^{5

6}

Affiliations

¹ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
² Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Science, BGI-Research, Qingdao 266555, China.
³ HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
⁴ College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
⁵ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁶ Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
⁷ Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.

Abstract

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.

Keywords: Biological sciences; Cancer; Omics.