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. 2021 Nov;80(11):1494-1497.
doi: 10.1136/annrheumdis-2021-220256. Epub 2021 May 17.

Single cell and spatial transcriptomics in human tendon disease indicate dysregulated immune homeostasis

Moeed Akbar  1 , Lucy MacDonald  1   2 , Lindsay A N Crowe  1 , Konstantin Carlberg  3 , Mariola Kurowska-Stolarska  1   2 , Patrik L Ståhl  3 , Sarah J B Snelling  4 , Iain B McInnes  1   2 , Neal L Millar  5
Affiliations

Single cell and spatial transcriptomics in human tendon disease indicate dysregulated immune homeostasis

Moeed Akbar et al. Ann Rheum Dis. 2021 Nov.
No abstract available

Keywords: arthritis; inflammation; tendinopathy.

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Conflict of interest statement

Competing interests: KC and PS are scientific consultants to 10x Genomics.

Figures

Figure 1
Figure 1
Cell composition and interactions of healthy and diseased human tendon. (A) Normal (n=4, human hamstring tendon) and diseased (tendinopathy, n=5, human supraspinatus tendon) human tendon were processed for single cell analysis using Chromium 10x 3′DEG chemistry. Infographic shows number of donors and cells sequenced. Uniform manifold approximation and projection (UMAP) embedding of 22 124 single cells delineating endothelial, immune, stromal tenocyte and stromal mural cells with marker genes. (B) Stromal cells of the tendon. UMAP embedding with gene markers and distribution of seven delineated stromal cell populations from human tendons; mural tenocyte (mT), normal tenocyte1 (nT1), normal tenocyte2 (nT2), diseased tenocyte1 (dT1), diseased tenocyte2 (dT2), diseased tenocyte3 (dT3) and diseased cycling tenocytes (dTc). (C) Immune cells of the tendon. UMAP embedding with gene markers and distribution of 6 delineated immune cell populations from human tendons; dendritic cells (DC), macrophage1 (Macro1), macrophage1 (Macro2), cycling macrophage (Macro-C), T-Cells1 (T-Cell1) and T-Cells2 (T-Cell2). (D) Endothelial cells (EC) of the tendon. UMAP embedding with gene markers and distribution of seven delineated EC populations from human tendons; CD36 high EC (CD36EC), E-Selectin EC (CD62eEC), collagen 4 vessel EC (COL4aEC), immune-like EC (ImmuneEC), LYVE1 positive EC (LYVE1EC) and SEMA3G positive EC (SEMA3GEC). (E) Tenocyte–immune interactions in tendon (n=3 healthy, vs 4 diseased). Predicted cell–cell interactions using CellphoneDB statistical framework on human tendon immune and stromal cells. Selected ligand receptor interactions showing APP and MIF ligand–receptor pairs in tendon stromal and immune cells. Mean of combined gene expression of interaction pairs (Log2 mean) and p value of specificity of interactions. Violin plots of APP and MIF expression in tendon stromal cells from healthy (pink) and diseased (green) tendon. Spatial expression (log2FC) of stromal APP and macrophage LYVE1 in normal human tendon and stromal MIF and macrophage CD74 in tendinopathic tendon visualised on 10x Genomics visium data, boxes highlight areas of coexpression. Violin plots of LYVE1 and CD74 expression in immune cells from healthy (pink) and diseased (green) tendon. Biorender infographic summarising tenocyte–immune cell interactions in tendon disease. (F) EC–tenocyte interactions in tendon. Predicted cell–cell interactions using CellphoneDB statistical framework on selected human tendon endothelial and stromal cells. Ligand–receptor interactions showing NOTCH3 ligand–receptor pairs in tendon endothelial and stromal cells. Mean of combined gene expression of interaction pairs (Log2 mean) and p value of specificity of interactions. Violin plots of NOTCH3 and JAG1 expression in tendon stromal and ECs, respectively from healthy (pink) and diseased (green) tendon. Spatial expression (log2FC) of NOTCH3 and MCAM from mural tenocytes and SEMA3G and JAG1 from SEMA3GEC’s in human diseased tendon visualised on 10x Genomics visium data, boxes highlight areas of coexpression. Biorender graphic of predicted SEMA3GEC and mT interaction in human tendon.
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