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Comparative analyses of erythroid cells from ES cells and cord blood CD34+ cells reveal mechanisms for defective expansion and enucleation of ES cell-derived erythroid cells

ABSTRACT: We used both RNA-seq and ATAC-seq analyses to uncovered mechanisms for the limited expansion and impaired enucleation in ES CD34+ cell-derived orthochromatic erythroblasts

ORGANISM(S): Homo sapiens

PROVIDER: GSE179778 | GEO | 2022/03/31

REPOSITORIES: GEO

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Comparative analyses of erythroid cells from ES cells and cord blood CD34+ cells reveal mechanisms for defective expansion and enucleation of ES cell-derived erythroid cells

Project description:Comparative analyses of erythroid cells from ES cells and cord blood CD34+ cells reveal mechanisms for defective expansion and enucleation of ES cell-derived erythroid cells

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Alpha 4 integrin deficiency in human CD34+ cells engenders a precocious erythroid differentiation ,but inhibits enucleation.

Project description:The functional impact of integrin expression in erythropoiesis has been previously emphasized through its decisive influence on erythroid cell-microenvironmental (matrix and cellular) interactions especially under conditions of stress. Beyond that in several in vitro studies the relationship between the two erythroid integrins, a4 and a5, has been incongruous in terms of a proliferative support, either synergistic or antagonistic, whereas a dominant influence of a4 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 present study we have cultured human CD34+ progenitor cells with induced deficiency of a4 integrin (shRNAa4) 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 documented that early proliferative expansion in cells lacking a4 expression is significantly limited, but, although erythroid differentiation can proceed normally to terminal stages, their enucleation is drastically impaired. This novel aspect of a4 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.

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