α4-Integrin deficiency in human CD34+ cells engenders precocious erythroid differentiation but inhibits enucleation

The functional impact of integrin expression in erythropoiesis has been previously emphasized through its decisive influence on erythroid cell-microenvironment (matrix and cellular) interactions, especially under conditions of stress. Beyond that, in several in vitro studies the relationship between the two erythroid integrins, alpha 4 and alpha 5, has been incongruous in terms of a proliferative support, either synergistic or antagonistic, whereas a dominant influence of alpha 4 integrin on terminal erythropoiesis in vitro and in vivo has been consistently emphasized. However, the specific cellular and molecular details of this effect have not been defined, especially for human cells. In the study described here, we cultured human CD34(+) progenitor cells with induced deficiency of alpha 4 integrin (shRNA alpha 4) under erythroid differentiation conditions, in which expanded erythroid progenitor cells are directed to terminal erythroid maturation stages in the absence of any microenvironmental influence. Our data indicate that early proliferative expansion in cells lacking alpha 4 expression is significantly limited, but although erythroid cell differentiation can proceed normally to terminal stages, their enucleation is drastically impaired. This novel aspect of alpha 4 integrin participation in the enucleation process in vitro resonates on the lack of in vivo enucleation of primitive erythroid cells lacking any integrin expression but affecting adult cells only under stress conditions. (C)& nbsp;2022 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.& nbsp;