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

• Published in: Cell stem cell Vol. 24; no. 1; pp. 183 - 192.e8
• Main Authors: Jones, Kyle B., Furukawa, Sachiko, Marangoni, Pauline, Ma, Hongfang, Pinkard, Henry, D’Urso, Rebecca, Zilionis, Rapolas, Klein, Allon M., Klein, Ophir D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-01-2019
• Subjects: Animals; Bmi1, single-cell RNA-seq; buccal mucosa; 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; oral epithelium; Polycomb Repressive Complex 1 - physiology; Proto-Oncogene Proteins - physiology; Single-Cell Analysis - methods; stem cell; Stem Cells - cytology; Stem Cells - metabolism; tongue; Transcriptome; buccal mucosa; stem cell; oral epithelium; tongue; Bmi1, single-cell RNA-seq
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2018.10.015

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.
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•Oral mucosal progenitor cells are located in the basal layer and proliferate rapidly•Bmi1 is expressed by nearly all basal layer cells, including oral mucosal progenitors•Progenitors undergo population-asymmetric self-renewal with neutral drift dynamics•Single-cell RNA-seq reveals a continuum of cell maturation states in the basal layer
Jones et al. define the organization, cycling kinetics, and clonal dynamics of oral mucosal progenitor cells. They also show, via single-cell RNA sequencing, that the basal layer contains progenitor and post-mitotic cells at various stages of maturation, demonstrating basal layer heterogeneity and providing insights into localization of cell fate decisions.