Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat

Zishui Fang; Yao Tian; Cong Sui; Yaxin Guo; Xinyao Hu; Youhua Lai; Zhiqi Liao; Jie Li; Guihai Feng; Lei Jin; Kun Qian

doi:10.3389/fcell.2022.919731

Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat

Front Cell Dev Biol. 2022 Jul 22:10:919731. doi: 10.3389/fcell.2022.919731. eCollection 2022.

Authors

Zishui Fang¹, Yao Tian², Cong Sui¹, Yaxin Guo¹, Xinyao Hu¹, Youhua Lai¹, Zhiqi Liao¹, Jie Li¹, Guihai Feng², Lei Jin¹, Kun Qian¹

Affiliations

¹ Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Abstract

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell-cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell-cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell-cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell-cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell-cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell-cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.

Keywords: angiogenesis; cell communication network; endometrium; proliferation; single-cell sequencing.