Publication Date:
2016-12-02
Description:
Hematopoietic stem cell (HSCs) are commonly isolated by using cell surface markers in order to study their hierarchy and functional properties. However, even with the most rigorous methods of isolation, subsets of HSCs likely exhibit functional heterogeneity. We have found that F4/80, an adhesion G-protein coupled receptor well known as a macrophage marker, was expressed on an HSC subpopulation (50-60% of Lin− Sca1− cKit− CD150+ CD34− CD135− cells) in the bone marrow. Interestingly, F4/80 was not expressed on HSCs that have egressed in the blood and on only a small fraction (3%) of splenic HSCs. To evaluate the function of the HSC subset expressing F4/80, we transplanted competitively 200 F4/80+ or F4/80− HSCs using CD45.1/2 congenic system. We found that F4/80+ HSCs exhibited a lower engraftment potential compared to F4/80− HSCs at 16 weeks after transplantation (19.7±4.8% and 37.1±4.5% donor contribution, respectively, P=0.025), although both HSC subsets were able to sustain mixed chimerism for myeloid, B and T cells without significant alteration in lineage bias. Since F4/80+ HSCs were not found in extramedullary tissues (blood or spleen), we tested whether they could be mobilized following G-CSF or CXCR4 antagonist (AMD3100) treatment. Interestingly, F4/80+ HSCs were still retained in the bone marrow after either G-CSF- or AMD3100-induced mobilization whereas F4/80− HSCs were mobilized efficiently. However, the frequency of bone marrow F4/80+ HSCs was reduced in G-CSF-treated animals (3.3-fold, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink