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Genes Dev. 2019 Nov 1;33(21-22):1457-1459. doi: 10.1101/gad.332791.119.

Hippo signaling does it again: arbitrating cardiac fibroblast identity and activation.

Author information

1
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA.
2
Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

Abstract

The Hippo pathway is an evolutionarily conserved kinase cascade that is fundamental for tissue development, homeostasis, and regeneration. In the developing mammalian heart, Hippo signaling regulates cardiomyocyte numbers and organ size. While cardiomyocytes in the adult heart are largely postmitotic, Hippo deficiency can increase proliferation of these cells and affect cardiac regenerative capacity. Recent studies have also shown that resident cardiac fibroblasts play a critical role in disease responsiveness and healing, and in this issue of Genes and Development, Xiao and colleagues (pp. 1491-1505) demonstrate that Hippo signaling also integrates the activity of fibroblasts in the heart. They show that Hippo signaling normally maintains the cardiac fibroblast in a resting state and, conversely, its inactivation during disease-related stress results in a spontaneous transition toward a myofibroblast state that underlies fibrosis and ventricular remodeling. This phenotypic switch is associated with increased cytokine signaling that promotes nonautonomous resident fibroblast and myeloid cell activation.

KEYWORDS:

Hippo signaling; cell state transitions; epigenomics; fibrosis; macrophages; myofibroblast; tissue homeostasis; myocardial infarction; single-cell RNA-seq

PMID:
31676733
PMCID:
PMC6824471
[Available on 2020-05-01]
DOI:
10.1101/gad.332791.119
[Indexed for MEDLINE]

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