Cell Stem Cell
Volume 25, Issue 6, 5 December 2019, Pages 814-829.e6
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Article
Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress

https://doi.org/10.1016/j.stem.2019.11.005Get rights and content
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Highlights

  • Oral epithelia are maintained by both delamination and oriented cell divisions

  • The hard palate contains a slow-cycling population residing in the junctional zone

  • Lrig1+ clones are biased to self-renew and Igfbp5+ clones to differentiate

  • Lrig1+ slow-cycling junctional zone stem cells are stress responsive

Summary

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

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

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