Quantitative Clonal Analysis and Single-Cell Transcriptomics Reveal Division Kinetics, Hierarchy, and Fate of Oral Epithelial Progenitor Cells

Cell Stem Cell. 2019 Jan 3;24(1):183-192.e8. doi: 10.1016/j.stem.2018.10.015. Epub 2018 Nov 21.


The oral mucosa is one of the most rapidly dividing tissues in the body and serves as a barrier to physical and chemical insults from mastication, food, and microorganisms. Breakdown of this barrier can lead to significant morbidity and potentially life-threatening infections for patients. Determining the identity and organization of oral epithelial progenitor cells (OEPCs) is therefore paramount to understanding their roles in homeostasis and disease. Using lineage tracing and label retention experiments, we show that rapidly dividing OEPCs are located broadly within the basal layer of the mucosa throughout the oral cavity. Quantitative clonal analysis demonstrated that OEPCs undergo population-asymmetrical divisions following neutral drift dynamics and that they respond to chemotherapy-induced damage by altering daughter cell fates. Finally, using single-cell RNA-seq, we establish the basal layer population structure and propose a model that defines the organization of cells within the basal layer.

Keywords: Bmi1, single-cell RNA-seq; buccal mucosa; oral epithelium; stem cell; tongue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Division
  • Cell Lineage*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Female
  • Homeostasis
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mouth Mucosa / cytology*
  • Mouth Mucosa / metabolism
  • Polycomb Repressive Complex 1 / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Single-Cell Analysis / methods*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcriptome


  • Bmi1 protein, mouse
  • Proto-Oncogene Proteins
  • Polycomb Repressive Complex 1