دورية أكاديمية
Decoding myofibroblast origins in human kidney fibrosis.
العنوان: | Decoding myofibroblast origins in human kidney fibrosis. |
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المؤلفون: | Kuppe C; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Ibrahim MM; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.; Bayer Pharma AG, Berlin, Germany., Kranz J; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.; Department of Urology and Paediatric Urology, St Antonius Hospital, Eschweiler, Germany.; Department of Urology, Kidney Transplantation Centre, Martin-Luther-University, Halle, Germany., Zhang X; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Ziegler S; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Perales-Patón J; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, BioQuant, Heidelberg, Germany.; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany., Jansen J; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands., Reimer KC; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.; Department of Cell Biology, Institute for Biomedical Technologies, RWTH Aachen University, Aachen, Germany., Smith JR; Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Dobie R; Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Wilson-Kanamori JR; Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Halder M; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Xu Y; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Kabgani N; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Kaesler N; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Klaus M; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Gernhold L; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Puelles VG; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Anatomy and Developmental Biology, Monash Biomedical Discovery Institute, Monash University, Melbourne, Victoria, Australia., Huber TB; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Boor P; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.; Department of Pathology, RWTH Aachen University, Aachen, Germany., Menzel S; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany., Hoogenboezem RM; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Bindels EMJ; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Steffens J; Department of Urology and Paediatric Urology, St Antonius Hospital, Eschweiler, Germany., Floege J; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany., Schneider RK; Department of Cell Biology, Institute for Biomedical Technologies, RWTH Aachen University, Aachen, Germany.; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Saez-Rodriguez J; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, BioQuant, Heidelberg, Germany.; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany.; Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg University, Heidelberg, Germany., Henderson NC; Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Kramann R; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany. rkramann@gmx.net.; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany. rkramann@gmx.net.; Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. rkramann@gmx.net. |
المصدر: | Nature [Nature] 2021 Jan; Vol. 589 (7841), pp. 281-286. Date of Electronic Publication: 2020 Nov 11. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Cell Lineage*, Fibrosis/*pathology , Kidney Tubules/*pathology , Myofibroblasts/*pathology , Renal Insufficiency, Chronic/*pathology, Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Calcium-Binding Proteins/metabolism ; Case-Control Studies ; Cell Differentiation ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Female ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Male ; Mesoderm/cytology ; Mesoderm/pathology ; Mice ; Myofibroblasts/metabolism ; Pericytes/cytology ; Pericytes/pathology ; RNA-Seq ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Single-Cell Analysis ; Transcriptome |
مستخلص: | Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist 1-3 . The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood 1,2,4 . Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis. |
التعليقات: | Comment in: Nat Rev Nephrol. 2021 Mar;17(3):151. (PMID: 33268843) Comment in: Kidney Int. 2021 Jun;99(6):1259-1261. (PMID: 33647325) Comment in: J Urol. 2021 Aug;206(2):480-482. (PMID: 33975458) |
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معلومات مُعتمدة: | 104366/Z/14/Z United Kingdom WT_ Wellcome Trust; United Kingdom MRC_ Medical Research Council; 219542/Z/19/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; 677448 International ERC_ European Research Council |
المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (Calcium-Binding Proteins) 0 (NKD2 protein, human) EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) |
تواريخ الأحداث: | Date Created: 20201111 Date Completed: 20210225 Latest Revision: 20230127 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7611626 |
DOI: | 10.1038/s41586-020-2941-1 |
PMID: | 33176333 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4687 |
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DOI: | 10.1038/s41586-020-2941-1 |