Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes

Lin, Weiping; Zhou, Xuedong; Lei, Kai; Xu, Ruoshi; Zhang, X.; Xiong, Qing; Sheng, Rui; Song, Wenqiang; Liu, W.; Wang, Q.; Yuan, Quan

doi:10.1177/00220345221092752

Cited by 17 publications

(11 citation statements)

References 40 publications

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“…In our analysis, T cells consisted of 2.5% of the total immune cells isolated from the periodontium. Others have similarly analyzed Cd45+ immune cells isolated from the periodontium of mice via scRNAseq and showed a T cell fraction that was comparable 32 or markedly greater 33 to our T cell fraction. Identifying multiple T cell clusters in our data set may have been achieved by performing a second re-clustering analysis using a higher resolution of only T cells.…”

Section: Discussionmentioning

confidence: 52%

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Cantalupo,

Diacou,

Park

et al. 2023

Preprint

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Periodontal health is dependent on a symbiotic relationship of the host immune response with the oral microbiota. Pathologic shifts of the microbial plaque elicit an immune response that eventually leads to the recruitment and activation of osteoclasts and matrix metalloproteinases and the eventual tissue destruction that is evident in periodontal disease. Once the microbial stimulus is removed, an active process of inflammatory resolution begins. The goal of this work was to use scRNAseq to demonstrate the unique cellular immune response across three distinct conditions of periodontal health, disease, and resolution using mouse models. Periodontal disease was induced using a ligature model. Resolution was modeled by removing the ligature and allowing the mouse to recover. Immune cells (Cd45+) were isolated from the periodontium and analyzed via scRNAseq. Gene signature shifts across the three conditions were characterized and shown to be largely driven by macrophage and neutrophils during the periodontal disease and resolution conditions. Resolution of periodontal disease was characterized by the differential regulation of unique gene subsets. Clustering analysis characterized multiple cellular subpopulations within B Cells, macrophages, and neutrophils that demonstrated differential expansion and contraction across conditions of periodontal health, disease, and resolution. Interestingly, we identified a transcriptionally distinct macrophage subpopulation that expanded during the resolution condition and demonstrated an immunoregulatory gene signature. We identified a cell surface marker for this resolution-associated macrophage subgroup (Cd74) and validated the expansion of this subgroup during resolution via flow cytometry. This work presents a robust immune cell atlas for study of the immunological changes in the oral mucosa during three distinct conditions of periodontal health, disease, and resolution and it improves our understanding of the cellular and molecular markers that characterize health from disease for the development of future diagnostics and therapies.

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Section: Discussionmentioning

confidence: 52%

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Cantalupo,

Diacou,

Park

et al. 2023

Preprint

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show abstract

“…However, whether MGFs also possess SCC-like potential and participate in the regulation of periodontal homeostasis via taste transduction pathway has yet to be investigated. We first re-analyzed sequence data deposited in the GEO RNA-seq database ( 24 , 25 ). We found that the expression of Tas2r143 was only reported in 2 of the 6 RNA-seq databases, and only one of these databases reported the expression of Gnat3.…”

Section: Discussionmentioning

confidence: 99%

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Zhang,

Zhou,

Liu

et al. 2024

Front. Immunol.

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IntroductionCells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These “taste-like” cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. MethodsPublic RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3−/−) mice. ResultsThe expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3−/− mice. DiscussionGingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via “SCC-like” activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the “SCC-like” function of gingival fibroblasts.

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“…The gingival ILCs expressed Rorc , Il17a, and Il17f, but not Tbx21 and Gata3, indicating that they were ILC3s. Notably, recent clinical studies have reported the presence of ILCs in gingiva from human periodontitis patients ( Brown et al, 2018 ; Dutzan et al, 2016 ) and leptin receptor-deficient mice ( Wang et al, 2022 ), although their pathological contributions have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Mouse gingival single-cell transcriptomic atlas identified a novel fibroblast subpopulation activated to guide oral barrier immunity in periodontitis

Kondo

Gleason

Okawa

et al. 2023

eLife

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Chronic cardiovascular and metabolic diseases have been linked with oral inflammation in the tooth-supporting gingiva. Therefore, elucidating the mechanisms underlying development of gingival inflammation may hold critical insight into the pathogenesis of these debilitating non-communicable diseases. Here, we report a unique fibroblast subpopulation activated to guide oral inflammation (AG fibroblasts), identified in a single-cell RNA sequencing-based gingival cell atlas constructed from the mouse ligature-induced periodontitis model. Collagen-XIV-positive AG fibroblasts localized beneath gingival epithelium express chemokine ligands and Toll-like receptor-related molecules upon ligature placement, which were linked to receptors expressed by neutrophils and lymphocytes, including innate lymphoid cells (ILCs). We further identify ILCs as the primary source of proinflammatory interleukin-17 cytokines and show that cervical alveolar bone resorption is absent in Rag2-/-γc-/-, but not Rag2-/-, mice suggesting ILC3s mediate the human periodontitis-like phenotype. We therefore propose AG fibroblasts function as a previously unrecognized surveillant to orchestrate chronic gingival inflammation in periodontitis.

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Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes

Cited by 17 publications

References 40 publications

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Mouse gingival single-cell transcriptomic atlas identified a novel fibroblast subpopulation activated to guide oral barrier immunity in periodontitis

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