Single-cell RNA sequencing revealed cell landscape of tongue dorsal mucosa in rats with gastric intestinal metaplasia

TL;DR

This study uses single-cell RNA sequencing to show how changes in rat tongue tissue relate to stomach lining changes, revealing inflammation and altered cell communication.

Contribution

The novel use of scRNA-seq to link tongue mucosa changes with gastric intestinal metaplasia in rats.

Findings

Tongue mucosa in GIM rats showed increased immune cells and downregulated autophagy genes.

Downregulation of keratin and taste receptor genes suggests impaired tissue function and taste perception.

Reduced cell communication between mesenchymal stem cells and epithelial cells was observed in GIM rats.

Abstract

The formation of tongue coating is closely related with the differentiation of the lingual dorsal mucosa, and a great deal of evidence shows that the variation of tongue coating reflects the pathological and physiological state of the gastric mucosa. However, the detailed mechanism remains elusive. This study established a rat model of gastric intestinal metaplasia (GIM) with 2% sodium salicylate and 20 mmol/L of deoxycholate sodium, and used single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of tongue dorsal mucosa. In comparison to the control group, the tongue dorsal mucosa of GIM rats became grayish-white, and the histologic characteristics presented an uneven distribution of tongue papilla with many immune cells in the submucosal layer. The expressive levels of pro-inflammatory factors (IL-1β, IL-6, and IL-17) were significantly higher in GIM rats than in the control group. Stratified analysis revealed the significant downregulation of autophagy marker gene Map1lc3a in neutrophils and T cells, and the significant downregulation of cuproptosis marker gene Dlst in fibroblasts of the tongue dorsal mucosa in GIM rats. These changes were closely related to mucosal inflammation and impaired tissue barrier integrity. Significantly, the expression of several keratin genes (Krt7, Krt8, Krt13, Krt16, and Krt76) was significantly downregulated, as well as the expression of the bitter taste receptor gene Rtp4 and the sweet taste receptor gene Tas1r2 in the GIM rats. The data indicated that fewer cells entered regulated cell death in immune cells of tongue mucosa, a more active inflammatory response occurred, the keratinization of tongue dorsal mucosal cells was inhibited, and the taste perception function was weakened. The results bring new perspectives on tongue coating in the application of gastric disorders.

Characteristics of the tongue dorsum mucosal cell landscape in the rats with gastric intestinal metaplasia. The abundances of T cells, neutrophils, and macrophages were upregulated, and the autophagy marker gene Map1lc3a in T cells and neutrophils was downregulated, which indicated an actively inflammatory immune response. Downregulation of cuprotosis marker gene Dlst in fibroblasts suggested potential damage to the mucosal barrier. Meanwhile, the expression of bitter receptor Rtp4 and sweet receptor Tas1r2 in mesenchymal stem cells was downregulated. The cell communication ability was reduced, especially between mesenchymal stem cells and epithelial cells. In a word, the abnormal status of tongue dorsum mucosa may accompany the development of gastric intestinal metaplasia.

Characteristics of the tongue dorsum mucosal cell landscape in the rats with gastric intestinal metaplasia. The abundances of T cells, neutrophils, and macrophages were upregulated, and the autophagy marker gene Map1lc3a in T cells and neutrophils was downregulated, which indicated an actively inflammatory immune response. Downregulation of cuprotosis marker gene Dlst in fibroblasts suggested potential damage to the mucosal barrier. Meanwhile, the expression of bitter receptor Rtp4 and sweet receptor Tas1r2 in mesenchymal stem cells was downregulated. The cell communication ability was reduced, especially between mesenchymal stem cells and epithelial cells. In a word, the abnormal status of tongue dorsum mucosa may accompany the development of gastric intestinal metaplasia.

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