Characterization of normal and cancer stem-like cell populations in murine lingual epithelial organoids using single-cell RNA sequencing

Erik Johansson,Hiroo Ueno

doi:10.1038/s41598-021-01783-5

Abstract

The advances in oral cancer research and therapies have not improved the prognosis of patients with tongue cancer. The poor treatment response of tongue cancer may be attributed to the presence of heterogeneous tumor cells exhibiting stem cell characteristics. Therefore, there is a need to develop effective molecular-targeted therapies based on the specific gene expression profiles of these cancer stem-like cell populations. In this study, the characteristics of normal and cancerous organoids, which are convenient tools for screening anti-cancer drugs, were analyzed comparatively. As organoids are generally generated by single progenitors, they enable the exclusion of normal cell contamination from the analyses. Single-cell RNA sequencing analysis revealed that p53 signaling activation and negative regulation of cell cycle were enriched characteristics in normal stem-like cells whereas hypoxia-related pathways, such as HIF-1 signaling and glycolysis, were upregulated in cancer stem-like cells. The findings of this study improved our understanding of the common features of heterogeneous cell populations with stem cell properties in tongue cancers, that are different from those of normal stem cell populations; this will enable the development of novel molecular-targeted therapies for tongue cancer.

Highlights

The advances in oral cancer research and therapies have not improved the prognosis of patients with tongue cancer
The incidence of oral cancer in young patients is steadily increasing, independent of traditional risk factors such as tobacco and alcohol use. This increase is due to the rise of tongue and oropharyngeal carcinomas, in the latter case related to human papilloma virus (HPV) infection[2]
This study examined the effects of 4-nitroquinoline-1-oxide (4-NQO), a commonly used carcinogen to induce tongue cancer in mice that mimics the effects of tobacco use by promoting the formation of DNA adducts[1,7]

Summary

Introduction

The advances in oral cancer research and therapies have not improved the prognosis of patients with tongue cancer. The incidence of oral cancer in young patients is steadily increasing, independent of traditional risk factors such as tobacco and alcohol use This increase is due to the rise of tongue and oropharyngeal carcinomas, in the latter case related to human papilloma virus (HPV) infection[2]. Previous studies on the mutational landscape of 4-NQOinduced tumors revealed that common mutations in human tongue carcinomas, including Trp[53], Pik3ca, and Notch[1], were recapitulated in the mouse model[10]. This model was selected for this study

Objectives

Results

Conclusion