Oxygen concentration influences mRNA processing and expression of the cd34 gene

CD34 is a cell surface glycoprotein expressed on hematopoietic stem and progenitor cells that disappears with their maturation. This gene is transcribed in two alternatively spliced mRNAs that encode full length and truncated form of CD34 cell surface antigen. Some publications suggested that CD34 full length plays a role in the maintenance of their self renewal capacity. An examination of CD34 regulation by a low O2 concentration that ensures a better maintenance of stem cells may provide important insights into the molecular control of hematopoiesis. Using human cord blood CD34+ cells, we first compared the effect of short term (24 h) culture in hypoxia (1% O2) and normoxia (20% O2) on the expression of full length and truncated form of cd34 transcripts and on the expression of the CD34 antigen. Hypoxia maintained a larger quantity of cd34 full length transcripts and a higher cd34 full length/cd34 truncated form ratio than normoxia. After 72 h of culture at 1% and 20% O2, sorted CD34low sub-population from 1% O2 primary culture still contained more cd34 full length mRNAs than those from 20% O2, maintained better CD34 antigen expression during secondary culture at 20% O2 and contained more undifferentiated cells. This work provides the first evidence of the regulation of the cd34 gene by hypoxia resulting in a delayed higher and longer antigen expression by cord blood cells. We suggest that this phenomenon is related to the better maintenance of primitive stem cells in hypoxia.