In this paper published in Cell Stem Cell, we identified Gli1 as a marker for resident mesenchymal stem cells across organs (Kidney, Heart, Lung, Liver, Bone Marrow). Using lineage analysis, we show that chronic injury drives these cells to proliferate and differentiate into scar-secreting myofibroblasts. Rafael Kramann, the first author, then genetically ablated these Gli1+ progenitors before injury, and showed that this prevented kidney fibrosis, and rescued heart function in a model of cardiomyopathy.
These results validate resident MSC-like cells as a therapeutic target in fibrotic disease. We are now working to develop drugs that will prevent Gli1+ cells from differentiating into myofibroblasts, since these are candidate therapies for humans with diseases like chronic kidney disease, idiopathic pulmonary fibrosis, cirrhosis and heart failure. See a summary of the article from the Harvard Gazette here.