Expression of integrin a2 receptor in human cord blood CD341CD382CD901 stem cells engrafting long-term in nod/scid-il2rccnull mice

Abstract

Human hematopoietic stem cells reside in the CD341CD382CD901 population in cord blood and bone marrow. However, this cell fraction is heterogeneous, and the phenotype of the rare primitive stem cells remains poorly defined. We here report that primitive cord blood CD341CD382CD901 stem cells, with the ability to reconstitute NOD/SCID-IL2Rccnull (NSG) mice long-term, at 24 weeks after transplantation, can be prospectively isolated at an increased purity by using integrin a2 receptor as an additional stem cell marker. Using a limiting dilution transplantation assay, we found a highly significant enrichment of multilineage reconstituting stem cells in the CD341CD382CD901 cell fraction expressing the integrin a2 receptor, with a frequency of 1/29 cells, as compared to a frequency of 1/157 in the corresponding integrin a22 cells. In line with this, long-term reconstituting stem cells within the cord blood CD341CD382 cell population were significantly enriched in the integrin a21 fraction, while stem cells and progenitors reconstituting short-term, at 8-12 weeks, were heterogeneous in integrin a2 expression. Global gene expression profiling revealed that the lineage-marker negative (Lin2) CD341CD382CD901CD45RA2 integrin a21 cell population was molecularly distinct from the integrin a22 cell population and the more mature Lin2CD341CD382CD902CD45RA2 cell population. Our findings identify integrin a2 as a novel stem cell marker, which improves prospective isolation of the primitive human hematopoietic stem cells within the CD341CD382CD901 cell population for experimental and therapeutic stem cell applications. © 2012 AlphaMed Press.