Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis
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 junctiona...
| 出版年: | Nature Communications |
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| 主要な著者: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Nature Portfolio
2024-06-01
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| オンライン･アクセス: | https://doi.org/10.1038/s41467-024-49037-y |
| _version_ | 1850368307479183360 |
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| author | Quinn T. Easter Bruno Fernandes Matuck Germán 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 Inês Sequeira Hyun Koo Katarzyna M. Tyc Jinze Liu Kang I. Ko Sarah A. Teichmann Kevin M. Byrd |
| author_facet | Quinn T. Easter Bruno Fernandes Matuck Germán 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 Inês Sequeira Hyun Koo Katarzyna M. Tyc Jinze Liu Kang I. Ko Sarah A. Teichmann Kevin M. Byrd |
| author_sort | Quinn T. Easter |
| collection | DOAJ |
| container_title | Nature Communications |
| description | 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. |
| format | Article |
| id | doaj-art-e25d449cf5024f9e90cca5df87ff4c19 |
| institution | Directory of Open Access Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| spelling | doaj-art-e25d449cf5024f9e90cca5df87ff4c192025-08-19T23:02:31ZengNature PortfolioNature Communications2041-17232024-06-0115112310.1038/s41467-024-49037-ySingle-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitisQuinn T. Easter0Bruno Fernandes Matuck1Germán Beldorati Stark2Catherine L. Worth3Alexander V. Predeus4Brayon Fremin5Khoa Huynh6Vaishnavi Ranganathan7Zhi Ren8Diana Pereira9Brittany T. Rupp10Theresa Weaver11Kathryn Miller12Paola Perez13Akira Hasuike14Zhaoxu Chen15Mandy Bush16Xufeng Qu17Janice Lee18Scott H. Randell19Shannon M. Wallet20Inês Sequeira21Hyun Koo22Katarzyna M. Tyc23Jinze Liu24Kang I. Ko25Sarah A. Teichmann26Kevin M. Byrd27Lab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteLab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteParse BiosciencesThe Bioinformatics CROWellcome Sanger Institute, Wellcome Genome CampusThe Bioinformatics CRODepartment of Biostatistics, Virginia Commonwealth UniversitySchool of Computer Science, Carnegie Mellon UniversityBiofilm Research Laboratories, Center for Innovation & Precision Dentistry, School of Dental Medicine, University of PennsylvaniaCenter for Oral Immunobiology and Regenerative Medicine, Barts Centre for Squamous Cancer, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonLab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteLab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteAkoya Biosciences Inc.Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of HealthLab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteDepartment of Periodontics, School of Dental Medicine, University of PennsylvaniaRespiratory TRACTS Core, Marsico Lung Institute, University of North Carolina at Chapel HillVCU Massey Comprehensive Cancer Center, Bioinformatics Shared Resource Core, Virginia Commonwealth UniversityCraniofacial Anomalies & Regeneration Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMarsico Lung Institute, University of North Carolina at Chapel HillDivision of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel HillCenter for Oral Immunobiology and Regenerative Medicine, Barts Centre for Squamous Cancer, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBiofilm Research Laboratories, Center for Innovation & Precision Dentistry, School of Dental Medicine, University of PennsylvaniaDepartment of Biostatistics, Virginia Commonwealth UniversityDepartment of Biostatistics, Virginia Commonwealth UniversityDepartment of Periodontics, School of Dental Medicine, University of PennsylvaniaWellcome Sanger Institute, Wellcome Genome CampusLab of Oral & Craniofacial Innovation (LOCI), Department of Innovation & Technology Research, ADA Science & Research InstituteAbstract 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.https://doi.org/10.1038/s41467-024-49037-y |
| spellingShingle | Quinn T. Easter Bruno Fernandes Matuck Germán 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 Inês Sequeira Hyun Koo Katarzyna M. Tyc Jinze Liu Kang I. Ko Sarah A. Teichmann Kevin M. Byrd Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title | Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title_full | Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title_fullStr | Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title_full_unstemmed | Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title_short | Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis |
| title_sort | single cell and spatially resolved interactomics of tooth associated keratinocytes in periodontitis |
| url | https://doi.org/10.1038/s41467-024-49037-y |
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