Phosphodiesterase 2A (PDE2A) is a cAMP-cGMP hydrolyzing enzyme essential for mouse development and the knockout model () is embryonic lethal. Notably, livers of embryos at embryonic day 14.5 (E14.5) have extremely reduced size. Morphological, cellular and molecular analyses revealed loss of integrity in the liver niche that compromises the hematopoietic function and maturation. Hematopoietic cells isolated from 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 embryos. The increase of the intracellular cAMP level and of the inducible cAMP early repressor (ICER) in liver of embryos might explain the impairment of liver development by downregulating the expression of the anti-apoptotic gene Bcl2. In summary, we propose as an essential gene for integrity maintenance of liver niche and the accomplishment of hematopoiesis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215450 | PMC |
| http://dx.doi.org/10.3390/ijms21082902 | DOI Listing |
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