Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury
Dan Su, … , Steven Eliason, Brad A. Amendt
Dan Su, … , Steven Eliason, Brad A. Amendt
Published January 9, 2025
Citation Information: JCI Insight. 2025;10(1):e179815. https://doi.org/10.1172/jci.insight.179815.
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Research Article Cell biology Stem cells

Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury

Abstract

The oral mucosa undergoes daily insults, and stem cells in the epithelial basal cell layer regenerate gingiva tissue to maintain oral health. The Iroquois Homeobox 1 (IRX1) protein is expressed in the stem cell niches in human/mouse oral epithelium and mesenchyme under homeostasis. We found that Irx1+/– heterozygous (Het) mice have delayed wound closure, delayed morphological changes of regenerated epithelium, and defective keratinocyte proliferation and differentiation during wound healing. RNA-Seq analyses between WT and Irx1+/– mice at 3 days postinjury (dpi) found impaired epithelial migration and decreased keratinocyte-related genes upon injury. IRX1-expressing cells are found in the gingival epithelial basal cell layer, a stem cell niche for gingival maintenance. IRX1-expressing cells are also found in cell niches in the underlying stroma. IRX1 activates SOX9 in the transient amplifying layer to increase cell proliferation, and EGF signaling is activated to induce cell migration. Krt14CreERT lineage tracing experiments reveal defects in the stratification of the Irx1+/– HET mouse oral epithelium. IRX1 is primed at the base of the gingiva in the basal cell layer of the oral epithelium, facilitating rapid and scarless wound healing through activating SOX9 and the EGF signaling pathway.

Authors

Dan Su, Tadkamol Krongbaramee, Samuel Swearson, Yan Sweat, Mason Sweat, Fan Shao, Steven Eliason, Brad A. Amendt

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Figure 7

Irx1+/– mice have reduced regenerated epithelium and less KRT5+ cells in the RF at 3 dpi.

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Irx1+/– mice have reduced regenerated epithelium and less KRT5+ cells i...
(A) Representative IF staining of Irx1+/+ homeostatic gingiva in front of the first molar. KRT5 marks the basal layer of gingival epithelium as well as the junctional epithelium. (B) Representative IF staining of the regenerated epithelium in Irx1+/+. KRT5 marks the cells in the basal layer at the distal area and the cells in the regenerative front. (C) Representative IF staining of Irx1+/– homeostatic gingival in front of the first molar. KRT5 marks the basal layer of gingival epithelium as well as the junctional epithelium. (D) Representative IF staining of the regenerated epithelium in Irx1+/–. KRT5 marks the cells in the basal layer at the distal area and the cells in the regenerative front. The regenerative front is ~600 μm to the first molar. Image area covers the region of injury. Blue staining represents nuclei. White dashed lines demarcate the gingival epithelium and mesenchyme. Scale bar: 100 μm.