例如:"lncRNA", "apoptosis", "WRKY"

Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development.

Dev Cell. 2018 Apr 23;45(2):153-169.e6
Yang Xiao 1 , Matthew C Hill 2 , Min Zhang 3 , Thomas J Martin 4 , Yuka Morikawa 5 , Suya Wang 6 , Alexander R Moise 7 , Joshua D Wythe 8 , James F Martin 9
Yang Xiao 1 , Matthew C Hill 2 , Min Zhang 3 , Thomas J Martin 4 , Yuka Morikawa 5 , Suya Wang 6 , Alexander R Moise 7 , Joshua D Wythe 8 , James F Martin 9
+ et al

[No authors listed]

Author information
  • 1 Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
  • 2 Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • 3 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Shanghai Children's Medical Center, Shanghai 200127, China.
  • 4 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • 5 Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, TX 77030, USA.
  • 6 Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA.
  • 7 Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA; Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada.
  • 8 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
  • 9 Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: jfmartin@bcm.edu.

摘要


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. Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS: Hippo signaling, epicardium, fibroblast differentiation, single-cell RNA sequencing