Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting
Understanding the heterogeneity of Rheumatoid Arthritis (RA) and identifying therapeutic targets remain challenging using traditional bulk transcriptomics alone, as it lacks the spatial and protein-level resolution needed to fully capture disease and tissue complexities. In this study, we applied La...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Proteomes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-7382/13/2/17 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849425356636815360 |
|---|---|
| author | Xue Wang Fei Wang Archana S. Iyer Heather Knight Lori J. Duggan Yingli Yang Liang Jin Baoliang Cui Yupeng He Jan Schejbal Lucy A. Phillips Bohdan P. Harvey Sílvia Sisó Yu Tian |
| author_facet | Xue Wang Fei Wang Archana S. Iyer Heather Knight Lori J. Duggan Yingli Yang Liang Jin Baoliang Cui Yupeng He Jan Schejbal Lucy A. Phillips Bohdan P. Harvey Sílvia Sisó Yu Tian |
| author_sort | Xue Wang |
| collection | DOAJ |
| description | Understanding the heterogeneity of Rheumatoid Arthritis (RA) and identifying therapeutic targets remain challenging using traditional bulk transcriptomics alone, as it lacks the spatial and protein-level resolution needed to fully capture disease and tissue complexities. In this study, we applied Laser Capture Microdissection (LCM) coupled with mass spectrometry-based proteomics to analyze histopathological niches of the RA synovium, enabling the identification of protein expression profiles of the diseased synovial lining and sublining microenvironments compared to their healthy counterparts. In this respect, key pathogenetic RA proteins like membrane proteins (TYROBP, AOC3, SLC16A3, TCIRG1, and NCEH1), and extracellular matrix (ECM) proteins (PLOD2, OGN, and LUM) showed different expression patterns in diseased synovium compartments. To enhance our understanding of cellular dynamics within the dissected regions, we further integrated the proteomic dataset with single-cell RNA sequencing (scRNA-seq), and deduced cell type enrichment, including T cells, fibroblasts, NK cells, myeloid cells, B cells, and synovial endothelial cells. By combining high-resolution spatial proteomics and transcriptomic analyses, we provide novel insights into the molecular mechanisms driving RA, and highlight potential protein targets for therapeutic intervention. This integrative approach offers a more comprehensive view of RA synovial pathology, and mitigates the limitations of traditional bulk transcriptomics in target discovery. |
| format | Article |
| id | doaj-art-e5f7acf9d4434c24b259a43e560b99df |
| institution | Kabale University |
| issn | 2227-7382 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Proteomes |
| spelling | doaj-art-e5f7acf9d4434c24b259a43e560b99df2025-08-20T03:29:48ZengMDPI AGProteomes2227-73822025-05-011321710.3390/proteomes13020017Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic TargetingXue Wang0Fei Wang1Archana S. Iyer2Heather Knight3Lori J. Duggan4Yingli Yang5Liang Jin6Baoliang Cui7Yupeng He8Jan Schejbal9Lucy A. Phillips10Bohdan P. Harvey11Sílvia Sisó12Yu Tian13AbbVie, South San Francisco, CA 94080, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie, North Chicago, IL 60064, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie, Cambridge, MA 02139, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAAbbVie Bioresearch Center, Worcester, MA 01605, USAUnderstanding the heterogeneity of Rheumatoid Arthritis (RA) and identifying therapeutic targets remain challenging using traditional bulk transcriptomics alone, as it lacks the spatial and protein-level resolution needed to fully capture disease and tissue complexities. In this study, we applied Laser Capture Microdissection (LCM) coupled with mass spectrometry-based proteomics to analyze histopathological niches of the RA synovium, enabling the identification of protein expression profiles of the diseased synovial lining and sublining microenvironments compared to their healthy counterparts. In this respect, key pathogenetic RA proteins like membrane proteins (TYROBP, AOC3, SLC16A3, TCIRG1, and NCEH1), and extracellular matrix (ECM) proteins (PLOD2, OGN, and LUM) showed different expression patterns in diseased synovium compartments. To enhance our understanding of cellular dynamics within the dissected regions, we further integrated the proteomic dataset with single-cell RNA sequencing (scRNA-seq), and deduced cell type enrichment, including T cells, fibroblasts, NK cells, myeloid cells, B cells, and synovial endothelial cells. By combining high-resolution spatial proteomics and transcriptomic analyses, we provide novel insights into the molecular mechanisms driving RA, and highlight potential protein targets for therapeutic intervention. This integrative approach offers a more comprehensive view of RA synovial pathology, and mitigates the limitations of traditional bulk transcriptomics in target discovery.https://www.mdpi.com/2227-7382/13/2/17rheumatoid arthritislaser capture microdissectionuntargeted proteomicsmass spectrometrymulti-omics integrationscRNA-seq |
| spellingShingle | Xue Wang Fei Wang Archana S. Iyer Heather Knight Lori J. Duggan Yingli Yang Liang Jin Baoliang Cui Yupeng He Jan Schejbal Lucy A. Phillips Bohdan P. Harvey Sílvia Sisó Yu Tian Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting Proteomes rheumatoid arthritis laser capture microdissection untargeted proteomics mass spectrometry multi-omics integration scRNA-seq |
| title | Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting |
| title_full | Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting |
| title_fullStr | Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting |
| title_full_unstemmed | Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting |
| title_short | Integrative Spatial Proteomics and Single-Cell RNA Sequencing Unveil Molecular Complexity in Rheumatoid Arthritis for Novel Therapeutic Targeting |
| title_sort | integrative spatial proteomics and single cell rna sequencing unveil molecular complexity in rheumatoid arthritis for novel therapeutic targeting |
| topic | rheumatoid arthritis laser capture microdissection untargeted proteomics mass spectrometry multi-omics integration scRNA-seq |
| url | https://www.mdpi.com/2227-7382/13/2/17 |
| work_keys_str_mv | AT xuewang integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT feiwang integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT archanasiyer integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT heatherknight integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT lorijduggan integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT yingliyang integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT liangjin integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT baoliangcui integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT yupenghe integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT janschejbal integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT lucyaphillips integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT bohdanpharvey integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT silviasiso integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting AT yutian integrativespatialproteomicsandsinglecellrnasequencingunveilmolecularcomplexityinrheumatoidarthritisfornoveltherapeutictargeting |