| First Author | Xiao Y | Year | 2018 |
| Journal | Dev Cell | Volume | 45 |
| Issue | 2 | Pages | 153-169.e6 |
| PubMed ID | 29689192 | Mgi Jnum | J:263874 |
| Mgi Id | MGI:6191807 | Doi | 10.1016/j.devcel.2018.03.019 |
| Citation | Xiao Y, et al. (2018) Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development. Dev Cell 45(2):153-169.e6 |
| abstractText | During development, progenitors progress through transition states. The cardiac epicardium contains progenitors of essential non-cardiomyocytes. The Hippo pathway, a kinase cascade that inhibits the Yap transcriptional co-factor, controls organ size in developing hearts. Here, we investigated Hippo kinases Lats1 and Lats2 in epicardial diversification. Epicardial-specific deletion of Lats1/2 was embryonic lethal, and mutant embryos had defective coronary vasculature remodeling. Single-cell RNA sequencing revealed that Lats1/2 mutant cells failed to activate fibroblast differentiation but remained in an intermediate cell state with both epicardial and fibroblast characteristics. Lats1/2 mutant cells displayed an arrested developmental trajectory with persistence of epicardial markers and expanded expression of Yap targets Dhrs3, an inhibitor of retinoic acid synthesis, and Dpp4, a protease that modulates extracellular matrix (ECM) composition. Genetic and pharmacologic manipulation revealed that Yap inhibits fibroblast differentiation, prolonging a subepicardial-like cell state, and promotes expression of matricellular factors, such as Dpp4, that define ECM characteristics. |
