The frequency of multipotent CD133(+)CD45RA(-)CD34(+) hematopoietic stem cells is not increased in fetal liver compared to adult stem cell sources.

Publication Type:

Journal Article

Source:

Experimental hematology, Volume 44, Issue 6, p.502-507 (2016)

Abstract:

The cell surface marker CD133 has been used to describe a revised model of adult human hematopoiesis with hematopoietic stem cells and multipotent progenitors (HSCs/MPPs: CD133(+)CD45RA(-)CD34(+)) giving rise to a lympho-myeloid primed progenitor (LMPPs: CD133(+)CD45RA(+)CD34(+)) and an erythro-myeloid progenitor (EMPs: CD133(low)CD45RA(-)CD34(+)). Since adult and fetal hematopoietic stem and progenitor cells (HSPCs) differ in their gene expression profile, differentiation capabilities, and cell surface marker expression, we were interested whether the reported segregation of lineage potentials in adult human hematopoiesis would also apply to the human fetal liver (FL). CD133 expression was easily detected on human FL cells, and the defined hematopoietic subpopulations were similar to the findings with adult HSPCs. Fetal HSPCs were enriched for EMPs and HSCs/MPPs, which were primed towards erythro-myeloid differentiation. However, the frequency of multipotent CD133(+)CD45RA(-)CD34(+) HSPCs was much lower than previously reported and comparable to umbilical cord blood. We found that engraftment in NSG mice was mostly driven by LMPPs, confirming recent findings that repopulation in mice is not a unique feature of multipotent HSCs/MPPs. Thus, our data challenges the general assumption that the human FL contains a greater percentage of multipotent HSCs/MPPs than any adult HSC source, and the mouse model may have to be re-evaluated with regard to the type of readout it provides.