| Authors |
Kramann R, Schneider RK, DiRocco DP, Machado F, Fleig S, Bondzie PA, Henderson
JM, Ebert BL, Humphreys BD
|
| Submitted By |
Benjamin Humphreys on 3/4/2015 |
| Status |
Published |
| Journal |
Cell stem cell |
| Year |
2015 |
| Date Published |
1/8/2015 |
| Volume : Pages |
16 : 51 - 66 |
| PubMed Reference |
|
| 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-脽 (PDGFR脽)(+) 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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