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Volume 21
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10.3390/ijms21082902
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Article

PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis

by
Federica Barbagallo
1,†,
Valentina Rotilio
2,†,
Maria Rita Assenza
2,
Salvatore Aguanno
2,
Tiziana Orsini
3,
Sabrina Putti
3,
Andrea M. Isidori
1,
Andrea Lenzi
1,
Fabio Naro
2,
Luciana De Angelis
2,† and
Manuela Pellegrini
2,3,*,†
1
Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy
2
Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University, 00161 Rome, Italy
3
Institute of Biochemistry and Cell Biology, National Research Council, 00015 Monterotondo, Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(8), 2902; https://doi.org/10.3390/ijms21082902
Submission received: 7 April 2020 / Revised: 17 April 2020 / Accepted: 18 April 2020 / Published: 21 April 2020
(This article belongs to the Special Issue Role of Phosphodiesterase in Biology and Pathology)
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Abstract

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.
Keywords: phosphodiesterase 2A; fetal liver; cAMP; ICER; apoptosis; hematopoiesis phosphodiesterase 2A; fetal liver; cAMP; ICER; apoptosis; hematopoiesis

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MDPI and ACS Style

Barbagallo, F.; Rotilio, V.; Assenza, M.R.; Aguanno, S.; Orsini, T.; Putti, S.; Isidori, A.M.; Lenzi, A.; Naro, F.; De Angelis, L.; et al. PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis. Int. J. Mol. Sci. 2020, 21, 2902. https://doi.org/10.3390/ijms21082902

AMA Style

Barbagallo F, Rotilio V, Assenza MR, Aguanno S, Orsini T, Putti S, Isidori AM, Lenzi A, Naro F, De Angelis L, et al. PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis. International Journal of Molecular Sciences. 2020; 21(8):2902. https://doi.org/10.3390/ijms21082902

Chicago/Turabian Style

Barbagallo, Federica, Valentina Rotilio, Maria Rita Assenza, Salvatore Aguanno, Tiziana Orsini, Sabrina Putti, Andrea M. Isidori, Andrea Lenzi, Fabio Naro, Luciana De Angelis, and et al. 2020. "PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis" International Journal of Molecular Sciences 21, no. 8: 2902. https://doi.org/10.3390/ijms21082902

APA Style

Barbagallo, F., Rotilio, V., Assenza, M. R., Aguanno, S., Orsini, T., Putti, S., Isidori, A. M., Lenzi, A., Naro, F., De Angelis, L., & Pellegrini, M. (2020). PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis. International Journal of Molecular Sciences, 21(8), 2902. https://doi.org/10.3390/ijms21082902

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