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Cell Stem Cell. 2018 Nov 7. pii: S1934-5909(18)30496-X. doi: 10.1016/j.stem.2018.10.015. [Epub ahead of print]

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

Author information

1
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA.
2
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA; Section of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
3
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Plastic and Reconstructive Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China.
4
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Biological Imaging Development Center, University of California, San Francisco, San Francisco, CA, USA; Computational Biology Graduate Group, University of California, San Francisco, San Francisco, CA, USA.
5
Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
6
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
7
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: ophir.klein@ucsf.edu.

Abstract

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

PMID:
30472156
DOI:
10.1016/j.stem.2018.10.015

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