iScience (Jun 2024)
Molecular maps of synovial cells in inflammatory arthritis using an optimized synovial tissue dissociation protocol
- Sam G. Edalat,
- Reto Gerber,
- Miranda Houtman,
- Janine Lückgen,
- Rui Lourenço Teixeira,
- Maria del Pilar Palacios Cisneros,
- Tamara Pfanner,
- Tadeja Kuret,
- Nadja Ižanc,
- Raphael Micheroli,
- Joaquim Polido-Pereira,
- Fernando Saraiva,
- Swathi Lingam,
- Kristina Burki,
- Blaž Burja,
- Chantal Pauli,
- Žiga Rotar,
- Matija Tomšič,
- Saša Čučnik,
- João Eurico Fonseca,
- Oliver Distler,
- Ângelo Calado,
- Vasco C. Romão,
- Caroline Ospelt,
- Snežna Sodin-Semrl,
- Mark D. Robinson,
- Mojca Frank Bertoncelj
Affiliations
- Sam G. Edalat
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Reto Gerber
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland; Department of Molecular Life Sciences and SIB, Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland
- Miranda Houtman
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Janine Lückgen
- Team PTA, BioMed X Institute, 69120 Heidelberg, Germany
- Rui Lourenço Teixeira
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Center, 1649-028 Lisbon, Portugal
- Maria del Pilar Palacios Cisneros
- Team PTA, BioMed X Institute, 69120 Heidelberg, Germany
- Tamara Pfanner
- Team PTA, BioMed X Institute, 69120 Heidelberg, Germany
- Tadeja Kuret
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland; Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Nadja Ižanc
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland; Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Raphael Micheroli
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Joaquim Polido-Pereira
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Center, 1649-028 Lisbon, Portugal
- Fernando Saraiva
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Center, 1649-028 Lisbon, Portugal
- Swathi Lingam
- Team PTA, BioMed X Institute, 69120 Heidelberg, Germany
- Kristina Burki
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Blaž Burja
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland; Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Chantal Pauli
- Department of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland
- Žiga Rotar
- Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Matija Tomšič
- Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Saša Čučnik
- Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
- João Eurico Fonseca
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Center, 1649-028 Lisbon, Portugal
- Oliver Distler
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Ângelo Calado
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal
- Vasco C. Romão
- Instituto de Medicina Molecular (iMM) João Lobo Antunes, Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Faculdade de Medicina, University of Lisbon, 1649-028 Lisbon, Portugal; Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Center, 1649-028 Lisbon, Portugal
- Caroline Ospelt
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland
- Snežna Sodin-Semrl
- Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, 6000 Koper, Slovenia
- Mark D. Robinson
- Department of Molecular Life Sciences and SIB, Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland; Corresponding author
- Mojca Frank Bertoncelj
- Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich and University of Zurich, 8952 Schlieren, Switzerland; Team PTA, BioMed X Institute, 69120 Heidelberg, Germany; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 6
p. 109707
Abstract
Summary: In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters. This synovial cell map expanded the diversity of synovial cell types/states, detected synovial neutrophils, and broadened synovial endothelial cell classification. We revealed tissue-resident macrophage subsets with proposed matrix-sensing (FOLR2+COLEC12high) and iron-recycling (LYVE1+SLC40A1+) activities and identified fibroblast subsets with proposed functions in cartilage breakdown (SOD2highSAA1+SAA2+SDC4+) and extracellular matrix remodeling (SERPINE1+COL5A3+LOXL2+). Our study offers an efficient synovium dissociation method and a reference scRNA-seq resource, that advances the current understanding of synovial cell heterogeneity in inflammatory arthritis.
