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Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis.
- Source :
-
Cell stem cell [Cell Stem Cell] 2015 Jan 08; Vol. 16 (1), pp. 51-66. Date of Electronic Publication: 2014 Nov 20. - Publication Year :
- 2015
-
Abstract
- Mesenchymal stem cells (MSCs) reside in the perivascular niche of many organs, including kidney, lung, liver, and heart, although their roles in these tissues are poorly understood. Here, we demonstrate that Gli1 marks perivascular MSC-like cells that substantially contribute to organ fibrosis. In vitro, Gli1(+) cells express typical MSC markers, exhibit trilineage differentiation capacity, and possess colony-forming activity, despite constituting a small fraction of the platelet-derived growth factor-β (PDGFRβ)(+) cell population. Genetic lineage tracing analysis demonstrates that tissue-resident, but not circulating, Gli1(+) cells proliferate after kidney, lung, liver, or heart injury to generate myofibroblasts. Genetic ablation of these cells substantially ameliorates kidney and heart fibrosis and preserves ejection fraction in a model of induced heart failure. These findings implicate perivascular Gli1(+) MSC-like cells as a major cellular origin of organ fibrosis and demonstrate that these cells may be a relevant therapeutic target to prevent solid organ dysfunction after injury.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antigens metabolism
Aorta drug effects
Aorta pathology
Aorta physiopathology
Blood Vessels drug effects
Blood Vessels metabolism
Blood Vessels pathology
Bone Marrow Cells drug effects
Bone Marrow Cells metabolism
Cell Differentiation drug effects
Cell Lineage drug effects
Cells, Cultured
Colony-Forming Units Assay
Diphtheria Toxin pharmacology
Endothelial Cells cytology
Endothelial Cells drug effects
Endothelial Cells metabolism
Fibrosis metabolism
Heart Ventricles drug effects
Heart Ventricles pathology
Heart Ventricles physiopathology
Homeostasis drug effects
Humans
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells drug effects
Mesenchymal Stem Cells ultrastructure
Mice
Myofibroblasts cytology
Myofibroblasts metabolism
Neovascularization, Physiologic drug effects
Organ Specificity drug effects
Pericytes drug effects
Pericytes metabolism
Pericytes pathology
Proteoglycans metabolism
Receptor, Platelet-Derived Growth Factor beta metabolism
Stem Cell Niche drug effects
Zinc Finger Protein GLI1
Fibrosis pathology
Kruppel-Like Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-9777
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell stem cell
- Publication Type :
- Academic Journal
- Accession number :
- 25465115
- Full Text :
- https://doi.org/10.1016/j.stem.2014.11.004