Single-cell and Spatially Resolved Interactomics of Tooth-associated Keratinocytes in Periodontitis

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 14

PMID 38876998

Authors

Quinn T Easter

Bruno Fernandes Matuck

German Beldorati Stark

Catherine L Worth

Alexander V Predeus

Brayon Fremin

Khoa Huynh

Vaishnavi Ranganathan

Zhi Ren

Diana Pereira

Brittany T Rupp

Theresa Weaver

Kathryn Miller

Paola Perez

Akira Hasuike

Zhaoxu Chen

Mandy Bush

Xufeng Qu

Janice Lee

Scott H Randell

Shannon M Wallet

Ines Sequeira

Hyun Koo

Katarzyna M Tyc

Jinze Liu

Kang I Ko

Sarah A Teichmann

Kevin M Byrd

Affiliations

Soon will be listed here.

Abstract

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.

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