RNA Binding Protein PCBP1 Functions in the Endothelial-to-Hematopoietic Transition During Hematopoietic Stem Cell...

Two paralogous RNA-binding proteins, PCBP1 and PCBP2, are individually essential for mouse development. Pcbp2-null embryos lose viability at midgestation, whereas Pcbp1-null embryos have an earlier, peri-implantation lethality. Inactivation of each gene alone in the differentiating erythroid lineage failed to impact embryonic viability, whereas combined Pcbp1/Pcbp2 inactivation resulted in repression of erythroid/hematopoietic gene expression midgestation, decreased blood cell formation, and fetal demise. Here, we assess the impacts of individual and combined conditional inactivation of Pcbp1 and Pcbp2 in endothelial cells on embryonic hematopoietic stem and progenitor cell (HSPC) formation. Inactivation of Pcbp1 in endothelial cells is embryonic lethal and reduces the number of HSPCs, whereas loss of Pcbp2 has no impact. Combined deletion of Pcbp1 and Pcbp2 in endothelial cells results in a more severe phenotype than loss of Pcbp1 alone. These results demonstrate that although Pcbp1 is a major regulator of HSPC formation, the two genes have nonredundant roles in endothelial cells.