PMID- 29921943 OWN - NLM STAT- MEDLINE VI - 8 IP - 1 TI - Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics. PG - 9370 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 IS - 2045-2322 (Electronic) LID - 10.1038/s41598-018-27627-3 [doi] FAU - Lundmark, Anna AU - Lundmark A AUID- ORCID: 0000-0002-3655-3710 AD - Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Huddinge, Sweden. anna.lundmark@ki.se. FAU - Gerasimcik, Natalija AU - Gerasimcik N AD - Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Huddinge, Sweden. FAU - Båge, Tove AU - Båge T AD - Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Huddinge, Sweden. FAU - Jemt, Anders AU - Jemt A AD - Science for Life Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden. FAU - Mollbrink, Annelie AU - Mollbrink A AD - Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden. AD - Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. FAU - Salmén, Fredrik AU - Salmén F AD - Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. AD - Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Centre Utrecht, Cancer Genomics Netherlands, Utrecht, The Netherlands. FAU - Lundeberg, Joakim AU - Lundeberg J AUID- ORCID: 0000-0003-4313-1601 AD - Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. FAU - Yucel-Lindberg, Tülay AU - Yucel-Lindberg T AD - Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Huddinge, Sweden. tulay.lindberg@ki.se. IS - 2045-2322 (Linking) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Calcium-Binding Proteins) RN - 0 (Cytokines) RN - 0 (MZB1 protein, human) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Peptide) RN - 0 (X-Box Binding Protein 1) RN - 0 (XBP1 protein, human) RN - 0 (signal sequence receptor) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Biopsy MH - Calcium-Binding Proteins/genetics/metabolism MH - Cytokines/genetics/metabolism MH - Gene Expression Profiling MH - Gingiva/*metabolism MH - Humans MH - Immunohistochemistry MH - Membrane Glycoproteins/genetics/metabolism MH - Periodontitis/*metabolism MH - Periodontium/*metabolism MH - Receptors, Cytoplasmic and Nuclear/genetics/metabolism MH - Receptors, Peptide/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcriptome/genetics MH - X-Box Binding Protein 1/genetics/metabolism PMC - PMC6008462 DCOM- 20191010 LR - 20211204 DP - 20180619 DEP - 20180619 AB - Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue. Moreover, 92 genes were identified as significantly up-regulated in inflamed areas of the gingival connective tissue compared to non-inflamed tissue. Among these, immunoglobulin lambda-like polypeptide 5 (IGLL5), signal sequence receptor subunit 4 (SSR4), marginal zone B and B1 cell specific protein (MZB1), and X-box binding protein 1 (XBP1) were the four most highly up-regulated genes. These genes were also verified as significantly higher expressed in gingival tissue of patients with periodontitis compared to healthy controls, using reverse transcription quantitative polymerase chain reaction. Moreover, the protein expressions of up-regulated genes were verified in gingival biopsies by immunohistochemistry. In summary, in this study, we report distinct gene expression signatures within periodontitis-affected gingival tissue, as well as specific genes that are up-regulated in inflamed areas compared to non-inflamed areas of gingival tissue. The results obtained from this study may add novel information on the genes and cell types contributing to pathogenesis of the chronic inflammatory disease periodontitis.