{"id":{"repo_id":"uic","oai_identifier":"oai:figshare.com:article/32994182"},"canonical_url":"https://search.dev.ndltd.org/etd/uic/oai:figshare.com:article/32994182","repository":{"repo_id":"uic","name":"University of Illinois - Chicago","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"Single-cell Analysis of Structural and Immune Cell Interactions in Periodontitis","abstract":"BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues and can be conceptualized as a dysregulated, non-healing wound. While bulk transcriptomic studies have provided insight into inflammatory pathways, single-cell RNA sequencing (scRNA-seq) enables detailed characterization of cell-type–specific responses and coordinated interactions within the periodontal microenvironment. OBJECTIVE: This study aimed to compare the transcriptional landscapes of structural and immune cell populations in periodontitis versus healthy gingival tissues using single-cell analysis, with a focus on fibroblasts, endothelial cells, macrophages, and neutrophils, to identify shared pathways associated with impaired wound healing and chronic inflammation. METHODS: ScRNA-seq datasets of human periodontitis-associated and control gingival samples (GSE152042, GSE161267, GSE164241) were obtained from the NCBI Gene Expression Omnibus (GEO) database. R (v4.5.1) in RStudio (2025.05.1+513) was used to re-analyze datasets. Seurat (v5.1.0) was utilized for quality control, integration, and analysis of the datasets, including batch correction and data visualization. Cell clustering, cell type annotation, and differentially expressed gene (DEG) analyses were performed to identify transcriptional signatures in structural and immune cells. Pathway enrichment (EnrichR) and ligand–receptor interaction (CellChat) analyses were conducted to evaluate functional alterations and intercellular communication between structural and immune compartments. STRING was used to identify and characterize protein–protein interaction (PPI) networks. RESULTS: From a total of 105,574 cells, we subset 17,533 fibroblasts, 22,947 endothelial cells, 2,129 macrophages, and 1,836 neutrophils for analysis. Differential expression revealed shared upregulated genes across cell populations that formed interconnected PPI networks associated with oxidative stress (e.g., SOD2, HSPA1A) and inflammatory signaling, including IL-17 and NF-κB pathways (e.g., JUND, TNFAIP3, NFKB1, REL). Structural cells demonstrated transcriptional signatures consistent with extracellular matrix remodeling, vascular regulation, and stress adaptation, while immune cells exhibited sustained activation of inflammatory and cytokine-mediated pathways. Importantly, overlapping transcriptional programs across structural and immune cell populations suggest coordinated multicellular responses reflective of impaired resolution and persistent inflammatory signaling characteristic of chronic wound environments. CONCLUSION(S): Single-cell transcriptomic profiling revealed coordinated and interconnected alterations across structural and immune cell populations in periodontitis, supporting its characterization as a chronic, non-healing wound. The identification of shared inflammatory and stress-response pathways highlights the importance of intercellular communication in sustaining disease and suggests that targeting common molecular mechanisms across cell types may offer novel therapeutic strategies for periodontal regeneration and disease resolution.","abstract_html":"BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues and can be conceptualized as a dysregulated, non-healing wound. While bulk transcriptomic studies have provided insight into inflammatory pathways, single-cell RNA sequencing (scRNA-seq) enables detailed characterization of cell-type–specific responses and coordinated interactions within the periodontal microenvironment. OBJECTIVE: This study aimed to compare the transcriptional landscapes of structural and immune cell populations in periodontitis versus healthy gingival tissues using single-cell analysis, with a focus on fibroblasts, endothelial cells, macrophages, and neutrophils, to identify shared pathways associated with impaired wound healing and chronic inflammation. METHODS: ScRNA-seq datasets of human periodontitis-associated and control gingival samples (GSE152042, GSE161267, GSE164241) were obtained from the NCBI Gene Expression Omnibus (GEO) database. R (v4.5.1) in RStudio (2025.05.1+513) was used to re-analyze datasets. Seurat (v5.1.0) was utilized for quality control, integration, and analysis of the datasets, including batch correction and data visualization. Cell clustering, cell type annotation, and differentially expressed gene (DEG) analyses were performed to identify transcriptional signatures in structural and immune cells. Pathway enrichment (EnrichR) and ligand–receptor interaction (CellChat) analyses were conducted to evaluate functional alterations and intercellular communication between structural and immune compartments. STRING was used to identify and characterize protein–protein interaction (PPI) networks. RESULTS: From a total of 105,574 cells, we subset 17,533 fibroblasts, 22,947 endothelial cells, 2,129 macrophages, and 1,836 neutrophils for analysis. Differential expression revealed shared upregulated genes across cell populations that formed interconnected PPI networks associated with oxidative stress (e.g., SOD2, HSPA1A) and inflammatory signaling, including IL-17 and NF-κB pathways (e.g., JUND, TNFAIP3, NFKB1, REL). Structural cells demonstrated transcriptional signatures consistent with extracellular matrix remodeling, vascular regulation, and stress adaptation, while immune cells exhibited sustained activation of inflammatory and cytokine-mediated pathways. Importantly, overlapping transcriptional programs across structural and immune cell populations suggest coordinated multicellular responses reflective of impaired resolution and persistent inflammatory signaling characteristic of chronic wound environments. CONCLUSION(S): Single-cell transcriptomic profiling revealed coordinated and interconnected alterations across structural and immune cell populations in periodontitis, supporting its characterization as a chronic, non-healing wound. The identification of shared inflammatory and stress-response pathways highlights the importance of intercellular communication in sustaining disease and suggests that targeting common molecular mechanisms across cell types may offer novel therapeutic strategies for periodontal regeneration and disease resolution.","abstract_has_math":false,"creators":["Jessica Castillo (12568892)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-05-01T00:00:00Z","date_published":"2026-05-01T00:00:00Z","updated_at":"2026-07-27T21:33:44Z","subjects":["Humans"],"languages":[],"rights":["In Copyright"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.25417/uic.32994182.v1","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Jessica Castillo (12568892)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2026-05-01T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/Single-cell_Analysis_of_Structural_and_Immune_Cell_Interactions_in_Periodontitis/32994182"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Humans"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.25417/uic.32994182.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues and can be conceptualized as a dysregulated, non-healing wound. While bulk transcriptomic studies have provided insight into inflammatory pathways, single-cell RNA sequencing (scRNA-seq) enables detailed characterization of cell-type–specific responses and coordinated interactions within the periodontal microenvironment. OBJECTIVE: This study aimed to compare the transcriptional landscapes of structural and immune cell populations in periodontitis versus healthy gingival tissues using single-cell analysis, with a focus on fibroblasts, endothelial cells, macrophages, and neutrophils, to identify shared pathways associated with impaired wound healing and chronic inflammation. METHODS: ScRNA-seq datasets of human periodontitis-associated and control gingival samples (GSE152042, GSE161267, GSE164241) were obtained from the NCBI Gene Expression Omnibus (GEO) database. R (v4.5.1) in RStudio (2025.05.1+513) was used to re-analyze datasets. Seurat (v5.1.0) was utilized for quality control, integration, and analysis of the datasets, including batch correction and data visualization. Cell clustering, cell type annotation, and differentially expressed gene (DEG) analyses were performed to identify transcriptional signatures in structural and immune cells. Pathway enrichment (EnrichR) and ligand–receptor interaction (CellChat) analyses were conducted to evaluate functional alterations and intercellular communication between structural and immune compartments. STRING was used to identify and characterize protein–protein interaction (PPI) networks. RESULTS: From a total of 105,574 cells, we subset 17,533 fibroblasts, 22,947 endothelial cells, 2,129 macrophages, and 1,836 neutrophils for analysis. Differential expression revealed shared upregulated genes across cell populations that formed interconnected PPI networks associated with oxidative stress (e.g., SOD2, HSPA1A) and inflammatory signaling, including IL-17 and NF-κB pathways (e.g., JUND, TNFAIP3, NFKB1, REL). Structural cells demonstrated transcriptional signatures consistent with extracellular matrix remodeling, vascular regulation, and stress adaptation, while immune cells exhibited sustained activation of inflammatory and cytokine-mediated pathways. Importantly, overlapping transcriptional programs across structural and immune cell populations suggest coordinated multicellular responses reflective of impaired resolution and persistent inflammatory signaling characteristic of chronic wound environments. CONCLUSION(S): Single-cell transcriptomic profiling revealed coordinated and interconnected alterations across structural and immune cell populations in periodontitis, supporting its characterization as a chronic, non-healing wound. The identification of shared inflammatory and stress-response pathways highlights the importance of intercellular communication in sustaining disease and suggests that targeting common molecular mechanisms across cell types may offer novel therapeutic strategies for periodontal regeneration and disease resolution."]},{"key":"dc:title","label":"Title","values":["Single-cell Analysis of Structural and Immune Cell Interactions in Periodontitis"]}]}],"canonical_facts":{"dc:creator":["Jessica Castillo (12568892)"],"dc:date":["2026-05-01T00:00:00Z"],"dc:description":["BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues and can be conceptualized as a dysregulated, non-healing wound. While bulk transcriptomic studies have provided insight into inflammatory pathways, single-cell RNA sequencing (scRNA-seq) enables detailed characterization of cell-type–specific responses and coordinated interactions within the periodontal microenvironment. OBJECTIVE: This study aimed to compare the transcriptional landscapes of structural and immune cell populations in periodontitis versus healthy gingival tissues using single-cell analysis, with a focus on fibroblasts, endothelial cells, macrophages, and neutrophils, to identify shared pathways associated with impaired wound healing and chronic inflammation. METHODS: ScRNA-seq datasets of human periodontitis-associated and control gingival samples (GSE152042, GSE161267, GSE164241) were obtained from the NCBI Gene Expression Omnibus (GEO) database. R (v4.5.1) in RStudio (2025.05.1+513) was used to re-analyze datasets. Seurat (v5.1.0) was utilized for quality control, integration, and analysis of the datasets, including batch correction and data visualization. Cell clustering, cell type annotation, and differentially expressed gene (DEG) analyses were performed to identify transcriptional signatures in structural and immune cells. Pathway enrichment (EnrichR) and ligand–receptor interaction (CellChat) analyses were conducted to evaluate functional alterations and intercellular communication between structural and immune compartments. STRING was used to identify and characterize protein–protein interaction (PPI) networks. RESULTS: From a total of 105,574 cells, we subset 17,533 fibroblasts, 22,947 endothelial cells, 2,129 macrophages, and 1,836 neutrophils for analysis. Differential expression revealed shared upregulated genes across cell populations that formed interconnected PPI networks associated with oxidative stress (e.g., SOD2, HSPA1A) and inflammatory signaling, including IL-17 and NF-κB pathways (e.g., JUND, TNFAIP3, NFKB1, REL). Structural cells demonstrated transcriptional signatures consistent with extracellular matrix remodeling, vascular regulation, and stress adaptation, while immune cells exhibited sustained activation of inflammatory and cytokine-mediated pathways. Importantly, overlapping transcriptional programs across structural and immune cell populations suggest coordinated multicellular responses reflective of impaired resolution and persistent inflammatory signaling characteristic of chronic wound environments. CONCLUSION(S): Single-cell transcriptomic profiling revealed coordinated and interconnected alterations across structural and immune cell populations in periodontitis, supporting its characterization as a chronic, non-healing wound. The identification of shared inflammatory and stress-response pathways highlights the importance of intercellular communication in sustaining disease and suggests that targeting common molecular mechanisms across cell types may offer novel therapeutic strategies for periodontal regeneration and disease resolution."],"dc:identifier":["10.25417/uic.32994182.v1"],"dc:relation":["https://figshare.com/articles/thesis/Single-cell_Analysis_of_Structural_and_Immune_Cell_Interactions_in_Periodontitis/32994182"],"dc:rights":["In Copyright"],"dc:subject":["Humans"],"dc:title":["Single-cell Analysis of Structural and Immune Cell Interactions in Periodontitis"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T21:33:44Z"}