Erythroblasts secrete the nonclassical HLA-G molecule from primitive to definitive hematopoiesis

The initial steps of primitive hematopoiesis and endothelial vascular formation in the human embryo remain to be defined. Here, we report the identification of a novel marker, namely the nonclassical HLA-G class I molecule, which targets both primitive erythroid cells of the yolk sac and endothelial cells from developing vessels. Moreover, HLA-G was present in its soluble form in the erythropoietic lineage in all organs sustaining primitive to definitive erythropoiesis (ie, aorta-gonad-mesonephros, liver, spleen, and bone marrow). The alternatively spliced transcript coding the soluble HLA-G5 molecule was detected in erythroid cells. The corresponding intron 4-retaining 37-kDa HLA-G5 isoform was secreted from the erythroid progenitor stage to the reticulocyte but was lost in mature erythrocytes and in endothelial cells from differentiated vessels. This study constitutes the first description of an HLA class I antigen expression on the primitive erythroid lineage and provides a way of seeking both primitive and definitive erythropoiesis using HLA-G5. This new marker, previously known by its immunotolerogeneic properties, may be involved in erythroid differentiation, angiogenesis, or both.