Identification and functional analyses of stem cell niches during oral tissue development and regeneration
Creators: name: Su, Dan
Publisher: name: University of Iowa
Year: 2025
Subjects: gingival regeneration
Irx1
stratified epithelium
tooth development
Whsc1
public abstract

description: Oral health is the state of the mouth, teeth and orofacial structures that enables people to perform oral functions such as breathing, chewing and speaking. Having good oral health is one of the best indicators of overall health, well-being, and quality of life. Oral health varies over the life course from early life to old age, and can be affected by congenital factors, trauma, or bad oral hygiene, which will further develop into oral diseases. Approximately 3.5 million people are affected by oral diseases, which results in the increasing global burden of oral health conditions. Nowadays, a tool for oral tissue engineering and regenerative therapy has drawn both clinical and scientific attention, which highly involves stem/progenitor cells in the oral cavity. Thus, identification and functional analyses of stem cell niches during oral tissue development and regeneration are essential.
description: Dental health is one of the main factors that contribute to oral health. Tooth anomalies, is one of the most common congenital defects all around the world that can occur in both deciduous and permanent dentitions. It is defined as abnormalities that alters the size, shape, and numbers of teeth. These dental defects are mainly due to the defective development of the dental germ. Patients suffer from tooth anomalies need rather costly and challenging multidisciplinary treatments. Thus, studying the genetic regulations underpinning the tooth developmental program responsible for the condition is rather crucial. Wolf-Hirschhorn syndrome (WHS) is a developmental disorder attributed to a partial deletion on the short arm of chromosome 4, which has been reported related to tooth anomalies. Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a H3K36-specific methyltransferase that is deleted in every reported case of WHS. Mutation in this gene exhibited tooth anomalies in patients. In this study, we used mouse as a model, determined that Whsc1 expression was reduced in the mouse incisor and molar tooth germs as tooth development proceeds. We also found Whsc1 and Pitx2, the first transcription factor in tooth development, positively and reciprocally regulated each other through their promoters. MicroRNAs are known to regulate gene expression post-transcriptionally during development. We demonstrated that miR-23a/b and miR-24-1/2, which were known to be highly expressed in the mature tooth germ, directly targeted to Whsc1 and repressed its expression. Additionally, this miR cluster was negatively regulated by Pitx2. The expression of these two miRs and Whsc1 were negatively correlated during mouse mandibular development.
description: Gingiva, a pink-colored resilient tissue surrounding the teeth, also serves as a major contributor to oral health. It functions as a barrier to protect the deeper dental and periodontal tissues from trauma and infection. This effective protection is largely attributed to the rapid and scarless wound healing of gingival tissue upon injuries. As part of the oral mucosa, gingiva is primed with wound-activated gene signatures to facilitate the festinating wound healing resolution. However, the genetic and molecular mechanism underlying this process is still largely unknown. Our lab previously found Iroquois Homeobox 1 (IRX1/Irx1) expressed in the basal layer of gingival epithelium and cell populations in the mesenchyme in human samples. In the present study, we established a mouse gingival injury model to investigate the role of Irx1 in epithelial basal cells during gingival wound healing. By analyzing the wound healing progression and the basal cell activity during gingival wound healing, we demonstrated that Irx1 haploinsufficiency delays re-epithelialization, as indicated by delayed wound closure, delayed structural changes in regenerated epithelium and altered differentiation of keratinocytes. The transcriptomic analysis revealed a diminished wound-activated signature in the Irx1+/- regenerated epithelium at 3 dpi. In the study, Irx1 was identified as a new gene that is primed at the base of the gingiva, which may facilitate rapid and scarless wound healing through the EGF signaling pathway.