Table 1.
Summaries of studies applying scRNA-seq to osteoimmunology research in RA.
| Study subjects | Source of cells | Number of subjects | Cell analyzed | Findings | Method used | Date published | Reference |
|---|---|---|---|---|---|---|---|
| CIA mice and RA patients | Synovial tissue | RA patients (n = 23) | Murine CX3CR1hiLy6CintF4/8+I-A+/I-E+ macrophages (AtoMs)and human CX3CR1+HLA-DRhiCD11c+CD80-CD86+ cells | AtoMs are the osteoclast precursor-containing population in the pannus tissue, and FoxM1 constitutes a potential target for RA treatment. | scRNA-Seq | November 18, 2019 | [56] |
|
RA patients OA patients Healthy donors |
Synovial tissue and blood |
RA patients (n = 18) OA patients (n = 14) |
HBEGF+ inflammatory macrophages | These HBEGF+ macrophages may enhance the tissue destructive capacity of fibroblasts. | scRNA-Seq | May 8, 2019 | [58] |
| Early/active RA, treatment-refractory/active RA and RA in sustained remission, healthy donors | Synovial tissue | RA patients: naïve to treatment (n = 45), treatment-resistant (n = 31), in sustained clinical and ultrasound remission (n = 36) | MerTKpos TREM2high and MerTKposLYVE1pos macrophage | The relative proportions of these cells in RA may be a marker to predict the state of persistent remission vs. disease flare. |
scRNA-seq, multiparameter Flow cytometry, immunofluorescent staining |
June 29, 2020 | [59] |
| Chinese subjects underwent hip replacement surgery | Bone marrow | n = 2 | LEPRhiCD45lowBM-MSCs | These cells had the capacity to differentiate into osteocytes, chondrocytes, adipocytes, and terminal-stage quiescent cells. Some new markers for purification of human BM-MSC were identified. | scRNA-seq | October 11, 2021 | [63] |
| Mice | Bone marrow | NA | Mesenchymal progenitors at different stages | We find a unique cell type that expresses adipocyte markers but contains no lipid droplets. They play critical roles in maintaining marrow vasculature and suppressing bone formation. | scRNA-seq | April 14, 2020 | [64] |
| RA and OA patients | Synovial tissue | n = 51 | T cells, B cells, monocytes, and fibroblasts | We identified 18 unique cell populations and defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. | scRNA-seq, mass cytometry, bulk RNA-seq, and flow cytometry | May 6, 2019 | [27] |
| RA patients | PBMC and Synovial tissue |
ACPA+RAn = 10 ACPA-RA n = 10 |
CD45+hematopoietic cells | Up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA-RA; a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of ACPA-RA; DRB1/DRB5 conveys an increased risk of developing active disease in ACPA+RA | scRNA-seq, Immunohistoche mical staining | August 17, 2021 | [87] |
| RA patients and healthy indifiduals | Peripheral blood | n = 4 | RA-CCPPOS B cells | The expression of IL15R is enriched in citrulline-specific B cells within RA patients were capable of producing AREG | RNA-sequencing, aptamer-based SOMAscan assay, flow cytometry | February 23, 2019 | [88] |
| RA patients | Synovial tissue | n = 5 | Fibroblast | 13 transcriptomically distinct clusters were revealed. Previously uncharacterized fibroblast subpopulations were identified and their spatial location within the synovium was discerned. | A 3D-printed, low-cost droplet microfluidic control instrument | February 23, 2018 | [91] |
| RA and OA patients | Synovial tissue | NA | Synovium fibroblast | Seven fibroblast subsets with distinct surface protein phenotypes were identified. | Bulk transcriptomics of targeted subpopulations and single-cell transcriptomics | February 23, 2018 | [92] |
| Mouse models of resolving and persistent arthritis | Synovial tissue | NA | FAPα+ synovial fibroblast | The location and function of two FAPα+ synovial fibroblasts. | Single-cell transcriptional technologies | May 29, 2019 | [93] |
| Mice | Synovial tissue | NA | Fibroblast | Expression of the synovial lining markers gradually changes along the continuum of synovial fibroblast states. Endothelium-derived Notch signaling is a potential pathway for driving the differentiation of THY1 expressing fibroblasts. | Trajectory transcriptional analyses, single-cell RNA-seq datasets | July 2020 | [94] |
| RA patients and mice | Synovial tissue | NA | Fibroblast | NOTCH3 signaling drives both transcriptional and spatial gradients in fibroblasts and plays an important role in inflammation. | scRNA-seq and synovial tissue organoids | April 22, 2020 | [95] |
BM-MSC: Bone marrow derived mesenchymal stem cell; CIA: Collagen-induced arthritis; NA: Not applicable; OA: Osteoarthritis; PBMC: Peripheral blood mononuclear cells;RA: Rheumatoid arthritis; scRNA-Seq: single cell RNA sequencing; TH1: T helper 1.