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- W2801678858 startingPage "153" @default.
- W2801678858 abstract "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." @default.
- W2801678858 created "2018-05-17" @default.
- W2801678858 creator A5011247610 @default.
- W2801678858 creator A5039868182 @default.
- W2801678858 creator A5044954870 @default.
- W2801678858 creator A5063340496 @default.
- W2801678858 creator A5066966896 @default.
- W2801678858 creator A5070480193 @default.
- W2801678858 creator A5078851874 @default.
- W2801678858 creator A5080982128 @default.
- W2801678858 creator A5085334560 @default.
- W2801678858 date "2018-04-01" @default.
- W2801678858 modified "2023-10-17" @default.
- W2801678858 title "Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development" @default.
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