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Series GSE262446 Query DataSets for GSE262446
Status Public on May 17, 2024
Title DPSCs Regulate Epithelial-T Cell Interactions in Oral Submucous Fibrosis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Background: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options.
Methods: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy.
Results: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19+MIF+ epithelial cells and via epithelial-stromal crosstalk.
Conclusions: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
Overall design We performed scRNA-seq analysis with oral mucosa tissues from OSF patients and controls.
Contributor(s) Jiao K
Citation(s) 38650025
Submission date Mar 26, 2024
Last update date May 18, 2024
Contact name sy w
Organization name fmmu
Street address Changle West Road 145
City Xi‘an
ZIP/Postal code 710032
Country China
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (2)
GSM8169898 6-9-1nm
GSM8169899 LB
BioProject PRJNA1091880

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Supplementary file Size Download File type/resource
GSE262446_RAW.tar 191.2 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA

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