First Author | Barbagallo F | Year | 2020 |
Journal | Int J Mol Sci | Volume | 21 |
Issue | 8 | PubMed ID | 32326334 |
Mgi Jnum | J:346773 | Mgi Id | MGI:7618869 |
Doi | 10.3390/ijms21082902 | Citation | Barbagallo F, et al. (2020) PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis. Int J Mol Sci 21(8) |
abstractText | Phosphodiesterase 2A (PDE2A) is a cAMP-cGMP hydrolyzing enzyme essential for mouse development and the PDE2A knockout model (PDE2A(-/-)) is embryonic lethal. Notably, livers of PDE2A(-/-) embryos at embryonic day 14.5 (E14.5) have extremely reduced size. Morphological, cellular and molecular analyses revealed loss of integrity in the PDE2A(-/-) liver niche that compromises the hematopoietic function and maturation. Hematopoietic cells isolated from PDE2A(-/-) livers are instead able to differentiate in in vitro assays, suggesting the absence of blood cell-autonomous defects. Apoptosis was revealed in hepatoblasts and at the endothelial and stromal compartments in livers of PDE2A(-/-) embryos. The increase of the intracellular cAMP level and of the inducible cAMP early repressor (ICER) in liver of PDE2A(-/-) embryos might explain the impairment of liver development by downregulating the expression of the anti-apoptotic gene Bcl2. In summary, we propose PDE2A as an essential gene for integrity maintenance of liver niche and the accomplishment of hematopoiesis. |