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Cell Stem Cell. 2019 Dec 5;25(6):814-829.e6. doi: 10.1016/j.stem.2019.11.005.

Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress.

Author information

1
Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Division of Oral & Craniofacial Health Sciences, the University of North Carolina Adams School of Dentistry, Chapel Hill, NC 27599, USA.
2
Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
3
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
4
Centre for Stem Cells & Regenerative Medicine, King's College London, London E1 9RT, UK.
5
Department of Pediatrics and Institute for Human Genetics, Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Veterans Affairs Medical Center, Nashville, Vanderbilt University, TN 37212, USA.
7
Department of Pathology & Laboratory Medicine, the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: scott_williams@med.unc.edu.

Abstract

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an important model system to study epithelial stem cell populations and how they respond to tissue stresses.

KEYWORDS:

Igfbp5; Lrig1; label retention; lineage tracing; oral epithelium; oriented cell division; palate; soft diet; stem cell; wound healing

PMID:
31809739
PMCID:
PMC6925542
[Available on 2020-12-05]
DOI:
10.1016/j.stem.2019.11.005

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