Fig. 1: An integrated periodontitis atlas reveals important oral keratinocyte population roles in immune signaling.

a Specialized tissues support human teeth, including the periodontium, consisting of 1) gingiva (blue/box: epithelia; stroma), 2) periodontal ligament, and 3) mineralized tissues (cementum; alveolar bone). b Four single-cell RNA sequencing (scRNAseq) datasets were reprocessed for broad cell class comparison between studies. c The gingival epithelial attachment is a specialized transitional epithelium example, changing from non-keratinized alveolar mucosa (AM; if present), to keratinized attached gingiva (AG), altering expression profiles at the gingival margin (GM), then specializing in gingival sulcus and junctional epithelial keratinocytes (SK/JKs). d Each study was first integrated using Harmony and assigned Tier 1 cell type annotations. e Harmonized tier annotation was performed between epithelial, stromal, endothelial, neural, and immune cell populations. f Integrated UMAP and cell assignments and g cell signatures (Supplementary Data 1) were generated. Epithelial cells (blue) are highlighted. The entire dataset was uploaded to publicly-available CELLxGENE (cellxgene.cziscience.com/). SKs and JKs were grouped in the Tier 3 analysis as co-expressing Keratin 14 (KRT14) and Keratin 19 (KRT19). h Pseudobulk analysis of some differentially expressed genes (DEGs) in periodontitis using all keratinocytes (Tier 3 annotations) in volcano plots; full list, Supplementary Data 1. i Using CellPhoneDB, all Tier 3 cell types were analyzed for inferred receptor-ligand interactions; most frequent–bottom left. SK/JKs appear uniquely expressive of effector cytokines/other ligands compared to other keratinocytes (Supplementary Data 2). Abbreviations: ILCs Innate Lymphoid Cells, KCs Keratinocytes, VECs Vascular Endothelial Cells, VSM Vascular Smooth Muscle, LECs Lymphatic Endothelial Cells, Neut Neutrophils, Mast Muc, MM Masticatory (Keratinized) Mucosa, Lining Muc, LM Lining (Non-Keratinized) Mucosa, SB Suprabasal (Differentiated) Keratinocytes, Fib Fibroblast, AECs Arterial Endothelial Cells, PCV Postcapillary Venule, VECs Venule Endothelial Cells, Mac/Mono Macrophage/Monocytes, cDCs Conventional Dendritic Cells, pDC Plasmacytoid Dendritic Cells, Tc Cytotoxic T Cells, gdT Gamma Delta T Cells, Treg Regulatory T Cells, MAIT Mucosal Associated Invariant T Cells, Th Helper T Cells. Illustration from (a) created with BioIcons (image hosted at https://bioicons.com; tooth icon by Servier https://smart.servier.com/, licensed under CC-BY 3.0 Unported https://creativecommons.org/licenses/by/3.0/); illustration from (c) created with BioRender (https://www.biorender.com/). n = 34-sample, 105918-cells.