| First Author | Kanisicak O | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12260 | PubMed ID | 27447449 |
| Mgi Jnum | J:241168 | Mgi Id | MGI:5897942 |
| Doi | 10.1038/ncomms12260 | Citation | Kanisicak O, et al. (2016) Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun 7:12260 |
| abstractText | Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects in vivo. Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin(+) myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21(+) tissue-resident fibroblasts. |
