期刊
CELL STEM CELL
卷 16, 期 1, 页码 51-66出版社
CELL PRESS
DOI: 10.1016/j.stem.2014.11.004
关键词
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资金
- NIH/NIDDK [DK088923, DK103050]
- NIDDK Diabetic Complications Consortium [DK076169]
- Harvard Stem Cell Institute
- American Heart Association
- Deutsche Forschungsgemeinschaft [Kr 40731-1, Schn 1188/3-1]
- Evotec AG
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-beta (PDGFR beta)(+) 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.
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