Abstract
Hematopoietic stem cell (HSC) expansion with small molecules emerged as a promising avenue to improve the outcome of HSC transplantation, a procedure representing the main curative option for poor prognosis hematological diseases. HSC expansion also appears as a valuable resource for stem cell genetic engineering for therapeutic purposes. Unfortunately, the immuno-phenotype of expanded HSCs remains to be fully defined as some of the previously described HSC markers are not compatible with current culture conditions. Our group identified EPCR and ITGA3 as reliable markers that, when combined with currently known markers such as CD34 and CD90, define long-term reconstituting hematopoietic stem cells (LT-HSCs) in expanded cultures. In this article, we identify CEACAM1 as a novel culture-compatible surface marker of ex vivo expanded LT-HSCs that further refines the immuno-phenotype of these cells. CEACAM1-expressing cells show clonogenic and differentiation properties that are reminiscent of LT-HSCs in vitro, as well as long-term, serial and multilineage engraftment capacity in vivo. Sorting CEACAM1 expressing cells from the CD34+CD45RA-CD90+EPCR+ITGA3+ subset allows LT-HSC purification with incomparable purity, highlighting the value of this new marker.
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