Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing

Aging (Albany NY). 2021 Jan 10;13(5):6565-6591. doi: 10.18632/aging.202288. Epub 2021 Jan 10.

Abstract

Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myeloid cells and 3 types in endometrial epithelial cells were identified. Distinct CD8+ T cell states and different monocyte-macrophage populations were discovered, among which exhausted CD8+ T cells and macrophages were preferentially enriched in tumor. Both CD8+ T cells and macrophages comport with continuous activation model. Gene expression patterns examination and gene ontology enrichment analysis of endometrial epithelial cells revealed 3 subtypes: stem-like cells, secretory glandular cells and ciliated cells. Overall, our study presents a view of endometrial carcinoma at single-cell resolution that reveals the characteristics of endometrial epithelial cells in the endometrium, and provides a cellular landscape of the tumor immune microenvironment.

Keywords: endometrial carcinoma; endometrial epithelial cells; immune microenvironment; macrophage activation model; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology*
  • Endometrium / pathology*
  • Epithelial Cells / pathology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Lymphocytes / pathology
  • Macrophages
  • Myeloid Cells / pathology
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA*
  • Single-Cell Analysis

Substances

  • RNA, Messenger