Journal article
Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury
JCI insight, Vol.10(1), e179815
01/09/2025
DOI: 10.1172/jci.insight.179815
PMCID: PMC11721312
PMID: 39782692
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.
Details
- Title: Subtitle
- Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury
- Creators
- Dan Su - Carver Bible CollegeTadkamol Krongbaramee - University of IowaSamuel Swearson - Carver Bible CollegeYan Sweat - Harvard UniversityMason Sweat - Harvard UniversityFan Shao - University of IowaSteven Eliason - Carver Bible CollegeBrad A Amendt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.10(1), e179815
- DOI
- 10.1172/jci.insight.179815
- PMID
- 39782692
- PMCID
- PMC11721312
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Grant note
- NIH: DE013941, DE028527 University of Iowa
We thank members of the Amendt and Van Otterloo laboratories for their expertise and helpful discussions, and we thank previous lab members for contributing to the preliminary study. We thank Ling Yang and Kamal Rahmouni for generously sharing their surgery room and equipment, and we thank their lab members for schedule coordination. We thank BioRender.com for providing the contents that were used in the schematics of this paper. We also thank the Iowa Institute of Human Genetics (IIHG) Genomics Division for their help on sequencing. We thank the NIH (DE013941, DE028527 to BAA) and the University of Iowa for funding.
- Language
- English
- Date published
- 01/09/2025
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984772248602771
Metrics
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