The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development
Open accessAbstract
SUMMARY 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 composition (ECM). 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.
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Cites
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InfluentialHippo signaling impedes adult heart regeneration
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Cited by
The Hippo Signaling Pathway in Development and Disease
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The Role of the Epicardium During Heart Development and Repair
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Self-citation
Metadata
- Authors
- Xiao, Y., Hill, M. C., Zhang, M., Martin, T. J., Morikawa, Y., Wang, S., Moise, A. R., Wythe, J. D., & Martin, J. F.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 45
- Issue
- 2
- Pages
- 153-169.e6
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2801678858
- Cited by
- 183
- References
- 14
- FWCI
- 11.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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