| Title: |
Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis. |
| Authors: |
Easter, QT; Fernandes Matuck, B; Beldorati Stark, G; Worth, CL; Predeus, AV; Fremin, B; Huynh, K; Ranganathan, V; Ren, Z; Pereira, D; Rupp, BT; Weaver, T; Miller, K; Perez, P; Hasuike, A; Chen, Z; Bush, M; Qu, X; Lee, J; Randell, SH; Wallet, SM; Sequeira, I; Koo, H; Tyc, KM; Liu, J; Ko, KI; Teichmann, SA; Byrd, KM |
| Publication Year: |
2024 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Humans; Keratinocytes; Single-Cell Analysis; Periodontitis; Cell Communication; Cytokines; Periodontium; Immunity; Innate; In Situ Hybridization; Fluorescence; Male; Metagenomics; Bacteria; Female; Adult; Adaptive Immunity |
| Description: |
Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation. |
| Document Type: |
article in journal/newspaper |
| File Description: |
5016 - ? |
| Language: |
English |
| Relation: |
Nat Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/104043 |
| DOI: |
10.1038/s41467-024-49037-y |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/104043; https://doi.org/10.1038/s41467-024-49037-y |
| Rights: |
This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ; Copyright © 2024, The Author(s) |
| Accession Number: |
edsbas.B5C6A9D |
| Database: |
BASE |