Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, part...
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2025-01-01
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| author | Fei Wang Liang Jin Xue Wang Baoliang Cui Yingli Yang Lori Duggan Annette Schwartz Sterman Sarah M. Lloyd Lisa A. Hazelwood Neha Chaudhary Bhupinder Bawa Lucy A. Phillips Yupeng He Yu Tian |
| author_facet | Fei Wang Liang Jin Xue Wang Baoliang Cui Yingli Yang Lori Duggan Annette Schwartz Sterman Sarah M. Lloyd Lisa A. Hazelwood Neha Chaudhary Bhupinder Bawa Lucy A. Phillips Yupeng He Yu Tian |
| author_sort | Fei Wang |
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| description | Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions. Distinct fibroblast cell types are highly associated with fibroblast foci, and transitional alveolar type 2 and aberrant KRT5-/KRT17+ (KRT: keratin) epithelial cells are associated with morphologically normal alveoli in human IPF lungs. Furthermore, we employed laser capture microdissection-directed mass spectrometry to profile proteins. By comparing with another published similar dataset, common differentially expressed proteins and enriched pathways related to ECM structure organization and collagen processing were identified in fibroblast foci. Importantly, cell type enrichment results from innovative spatial proteomics and scRNA-seq data integration accord with those from spatial transcriptomics and scRNA-seq data integration, supporting the capability and versatility of the entire approach. In summary, we integrated spatial multi-omics with scRNA-seq data to identify disease-associated cell types and potential targets for novel therapies in IPF intervention. The approach can be further applied to other disease areas characterized by spatial heterogeneity. |
| format | Article |
| id | doaj-art-08cbcde23b07439b9bad039ffec631fb |
| institution | Kabale University |
| issn | 2227-7382 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Proteomes |
| spelling | doaj-art-08cbcde23b07439b9bad039ffec631fb2025-08-20T03:43:54ZengMDPI AGProteomes2227-73822025-01-01131310.3390/proteomes13010003Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF PathogenesisFei Wang0Liang Jin1Xue Wang2Baoliang Cui3Yingli Yang4Lori Duggan5Annette Schwartz Sterman6Sarah M. Lloyd7Lisa A. Hazelwood8Neha Chaudhary9Bhupinder Bawa10Lucy A. Phillips11Yupeng He12Yu Tian13Research & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie, South San Francisco, CA 94080, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie, North Chicago, IL 60064, USAResearch & Development, AbbVie, North Chicago, IL 60064, USAResearch & Development, AbbVie Cambridge Research Center, Cambridge, MA 02139, USAResearch & Development, AbbVie, North Chicago, IL 60064, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAResearch & Development, AbbVie, North Chicago, IL 60064, USAResearch & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USAIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions. Distinct fibroblast cell types are highly associated with fibroblast foci, and transitional alveolar type 2 and aberrant KRT5-/KRT17+ (KRT: keratin) epithelial cells are associated with morphologically normal alveoli in human IPF lungs. Furthermore, we employed laser capture microdissection-directed mass spectrometry to profile proteins. By comparing with another published similar dataset, common differentially expressed proteins and enriched pathways related to ECM structure organization and collagen processing were identified in fibroblast foci. Importantly, cell type enrichment results from innovative spatial proteomics and scRNA-seq data integration accord with those from spatial transcriptomics and scRNA-seq data integration, supporting the capability and versatility of the entire approach. In summary, we integrated spatial multi-omics with scRNA-seq data to identify disease-associated cell types and potential targets for novel therapies in IPF intervention. The approach can be further applied to other disease areas characterized by spatial heterogeneity.https://www.mdpi.com/2227-7382/13/1/3Idiopathic pulmonary fibrosisspatial transcriptomicslaser capture microdissectionspatial proteomicsmass spectrometryscRNA-seq |
| spellingShingle | Fei Wang Liang Jin Xue Wang Baoliang Cui Yingli Yang Lori Duggan Annette Schwartz Sterman Sarah M. Lloyd Lisa A. Hazelwood Neha Chaudhary Bhupinder Bawa Lucy A. Phillips Yupeng He Yu Tian Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis Proteomes Idiopathic pulmonary fibrosis spatial transcriptomics laser capture microdissection spatial proteomics mass spectrometry scRNA-seq |
| title | Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis |
| title_full | Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis |
| title_fullStr | Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis |
| title_full_unstemmed | Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis |
| title_short | Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis |
| title_sort | novel integration of spatial and single cell omics data sets enables deeper insights into ipf pathogenesis |
| topic | Idiopathic pulmonary fibrosis spatial transcriptomics laser capture microdissection spatial proteomics mass spectrometry scRNA-seq |
| url | https://www.mdpi.com/2227-7382/13/1/3 |
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