Human blood vessel organoids recapitulate key mechanisms of transition from vasculopathy to fibrosis in systemic sclerosis
Xiao, Y.; Hong, X.; Zhi, L.; Li, Y. N.; Regensburger, M.; Marxreiter, F.; Gorg, B.; Koziel, S.; Gyorfi, A. H.; Filla, T.; Bruch, P. M.; Tripal, P.; Adjaye, J.; Dietrich, S.; Winkler, J.; Distler, J. H. W.; Matei, A. E.
Show abstract
Systemic sclerosis (SSc) is an autoimmune disease that transitions from vasculopathy as an initiating pathogenic event to tissue fibrosis. The mechanisms of these transitions remain, however, poorly understood, mainly because complex multicellular human models of SSc vasculopathy are lacking. Here we characterized blood vessel organoids (BVOs) as a novel model system of vasculopathy in SSc. We demonstrate that exposure of SSc-BVOs to SSc serum triggers changes on epigenetic, mRNA and protein levels and recapitulates key pathogenic features of SSc vasculopathy, with shifts from angiogenic endothelial cell subsets to those undergoing endothelial-to-mesenchymal transition, loss of endothelial cells-pericytes interactions and profound angiogenic defects. The genetic predisposition of SSc donors and serum IgGs are required for the deleterious effects of SSc serum. We further validate SSc-BVOs as a human model system to evaluate candidate therapies targeting SSc microvasculopathy and use this system to provide evidence that {gamma}-secretase inhibition is a potential therapeutic approach.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Nuclear receptor subfamily 4A signaling as a key disease pathway of CD1c+ dendritic cell dysregulation in systemic sclerosis 96%
- Functional genomics in primary T cells and monocytes identifies mechanisms by which genetic susceptibility loci influence systemic sclerosis risk 94%
- Activin A-activated ALK4 induces pathogenic Th17 involvement in endothelial–mesenchymal transition in systemic lupus erythematosus-associated pulmonary arterial hypertension 93%
Similar papers in this journal
- Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mousemodel of Multiple Sulfatase Deficiency 90%
- M2 Macrophage Exosomes Reverse Cardiac Functional Decline in Mice with Diet-Induced Myocardial Infarction by Suppressing Type 1 Interferon Signaling in Myeloid Cells 90%
- GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis 89%
Similar papers in this journal
- IgG autoantibodies in bullous pemphigoid directly induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes: 92%
- Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers 92%
- Single Cell Transcriptomics of Fibrotic Lungs Unveils Aging-associated Alterations in Endothelial and Epithelial Cell Regeneration 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.