Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration

By W. Goessling, Trista E North, Sabine Loewer, Allegra M. Lord, S. Lee, Cristi L. Stoick-Cooper, G. Weidinger, M. Puder, G. Daley, R. Moon and 1 more. Cell, 2009

723 citations recorded by the source corpus.

Summary Interactions between developmental signaling pathways govern the formation and function of stem cells. Prostaglandin (PG) E2 regulates vertebrate hematopoietic stem cells (HSC). Similarly, the Wnt signaling pathway controls HSC self-renewal and bone marrow repopulation. Here, we show that wnt reporter activity in zebrafish HSCs is responsive to PGE2 modulation, demonstrating a direct interaction in vivo. Inhibition of PGE2 synthesis blocked wnt-induced alterations in HSC formation. PGE2 modified the wnt signaling cascade at the level of β-catenin degradation through cAMP/PKA-mediated stabilizing phosphorylation events. The PGE2/Wnt interaction regulated murine stem and progenitor populations in vitro in hematopoietic ES cell assays and in vivo following transplantation. The relationship between PGE2 and Wnt was also conserved during regeneration of other organ systems. Our work provides the first in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bb5abe74bd4aeb929cbbfe901d67dcd90fa93fb9

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In Molecular Biology

1. D. Lyden
2. Shahin Rafii
3. V. Mittal
4. Dingzhi Wang
5. R. Dubois
6. J. Talmadge
7. I. J. Fidler
8. Peter Carmeliet

Citations in the corpus

• Eicosanoids and cancer (2010, background): “and regulates growth and development of both embryonic haematopoietic stem cells and adult stem cells in several different organism”
• Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration (2010, positive): “Among the known hepatic trophogens 10 , 18 , 26 - 28 , the expression of Wnt2 and HGF, but not other trophogens expressed by LSECs, such as Wnt9B and thrombomodulin, were drastically diminished in Id1 −/− LSECs (Fig.”