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Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-1774-6058
Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 18975Article in journal (Refereed) Published
Abstract [en]

Lately it has become possible to analyze transcriptomic profiles in tissue sections with retained cellular context. We aimed to explore synovial biopsies from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients, using Spatial Transcriptomics (ST) as a proof of principle approach for unbiased mRNA studies at the site of inflammation in these chronic inflammatory diseases. Synovial tissue biopsies from affected joints were studied with ST. The transcriptome data was subjected to differential gene expression analysis (DEA), pathway analysis, immune cell type identification using Xcell analysis and validation with immunohistochemistry (IHC). The ST technology allows selective analyses on areas of interest, thus we analyzed morphologically distinct areas of mononuclear cell infiltrates. The top differentially expressed genes revealed an adaptive immune response profile and T-B cell interactions in RA, while in SpA, the profiles implicate functions associated with tissue repair. With spatially resolved gene expression data, overlaid on high-resolution histological images, we digitally portrayed pre-selected cell types in silico. The RA displayed an overrepresentation of central memory T cells, while in SpA effector memory T cells were most prominent. Consequently, ST allows for deeper understanding of cellular mechanisms and diversity in tissues from chronic inflammatory diseases.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 18975
National Category
Rheumatology and Autoimmunity
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URN: urn:nbn:se:kth:diva-266415DOI: 10.1038/s41598-019-55441-yISI: 000503044900002PubMedID: 31831833Scopus ID: 2-s2.0-85076349146OAI: oai:DiVA.org:kth-266415DiVA, id: diva2:1416202
Note

QC 20200322

Available from: 2020-03-22 Created: 2020-03-22 Last updated: 2020-03-22Bibliographically approved

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Carlberg, KonstantinLarsson, LudvigStåhl, Patrik

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