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. Byrd et al. show that stratified epithelia of the oral cavity display unusual proliferative heterogeneity, particularly in the hard palate region. A slow-cycling population residing in the junctional zone niche is LRIG1 HI, self-renews through planar symmetric divisions, responds to masticatory stress, and promotes wound healing.

Original languageEnglish
Pages (from-to)814-829.e6
JournalCell Stem Cell
Issue number6
Publication statusPublished - 5 Dec 2019


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


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