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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cell Lineage / physiology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Fluorescence
  • Immunohistochemistry
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mouth Mucosa / cytology*
  • Mouth Mucosa / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Wound Healing / physiology


  • Lrig1 protein, mouse
  • Membrane Glycoproteins
  • Nerve Tissue Proteins