{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:29:37Z","timestamp":1792056577070,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH), NIAMS division","award":["R01AR073516"],"award-info":[{"award-number":["R01AR073516"]}]},{"name":"National Institutes of Health (NIH), NIAMS division","award":["R01AR078560"],"award-info":[{"award-number":["R01AR078560"]}]},{"name":"Scleroderma Research Foundation","award":["R01AR073516"],"award-info":[{"award-number":["R01AR073516"]}]},{"name":"Scleroderma Research Foundation","award":["R01AR078560"],"award-info":[{"award-number":["R01AR078560"]}]},{"name":"Nancy Taylor Foundation for Chronic Diseases","award":["R01AR073516"],"award-info":[{"award-number":["R01AR073516"]}]},{"name":"Nancy Taylor Foundation for Chronic Diseases","award":["R01AR078560"],"award-info":[{"award-number":["R01AR078560"]}]},{"name":"Scleroderma Research Foundation","award":["R01AR073516"],"award-info":[{"award-number":["R01AR073516"]}]},{"name":"Scleroderma Research Foundation","award":["R01AR078560"],"award-info":[{"award-number":["R01AR078560"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist\u2019s annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist\u2019s assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.<\/jats:p>","DOI":"10.3390\/ijms25179182","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatial Transcriptomics Identifies Cellular and Molecular Characteristics of Scleroderma Skin Lesions: Pilot Study in Juvenile Scleroderma"],"prefix":"10.3390","volume":"25","author":[{"given":"Tianhao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0893-0603","authenticated-orcid":false,"given":"Deren","family":"Esencan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"UPMC Scleroderma Center, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-1296","authenticated-orcid":false,"given":"Claudia M.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"UMMG Department of Pathology, Miller School of Medicine, Medical Campus, University of Miami, 1550 NW 10th Ave. #118, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ju","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Hutchins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"UPMC Scleroderma Center, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7830-0949","authenticated-orcid":false,"given":"Anwesha","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"UPMC Scleroderma Center, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S.","family":"Torok","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children\u2019s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA"},{"name":"UPMC Scleroderma Center, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12519-019-00320-9","article-title":"Overview of Juvenile localized scleroderma and its management","volume":"16","author":"Li","year":"2020","journal-title":"World J. 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