Hematopoietic stem cells in human fetal liver selectively express CD49f.

Abstract

Identification of phenotypes of human hematopoietic cells that display long-term mature cell outputs in vitro and repopulating capability in immunodeficient mice has been important to anticipating the therapeutic potential of fresh harvests of bone marrow or cord blood before or after their physical or genetic manipulation. However, characterizing their key properties and strategies for their isolation from multiple sources at increasing cell purities and elucidating the mechanisms that regulate their ability to sustain mature blood cell production continues to be of major interest. Previous studies have shown that fetal and adult human cells with long-term blood cell output potential are highly enriched in their respective glycosylphosphatidylinositol (GPI)-anchored surface protein GPI80+ and CD49f+ subsets of a developmentally preserved CD45+CD34+CD38-CD45RA-CD90+ population. The so-called "GPI80" hematopoietic cells found in first-trimester human fetal liver are of particular interest because of their very high regenerative capability compared with their adult or even neonatal (cord blood) "CD49f" counterparts. Here, it was hypothesized that high regenerative activity of the GPI80+ cells could be further enriched within a CD49f+ subset. We now demonstrated that coexpression of CD49f within the GPI80+ population identifies a subset with reduced short-term myeloid colony-forming activity in semisolid medium and greater progeny outputs in both 12-week growth factor-supplemented stromal cocultures and in transplanted immunodeficient mice. These findings demonstrated that CD49f is a pervasive marker of human hematopoietic stem cells (HSCs) throughout ontogeny and aging.