Background: Beta-2-microglobulin (B2m)/MHC-I down regulation is a peculiar feature of fetal liver progenitors shared by two adult bone marrow derived stem cell subsets with proven ability to differentiate into hepatic cells, namely rat B2m-/Thy1+ cells (BDHSCs) and the multipotent adult progenitors (MAPCs). The phenotypic characterization of the MHC class I negative bone marrow compartment and the relationship between BDHSCs, MAPCs and well-characterized stem cell markers is however not known.
Methods: Multiparameter flow cytometric analysis of the MHC-I- compartment was performed with regard to mature hematopoietic (Glycophorin-A and CD45R) and stem cells markers (Thy1, cKit, IL-3R, CD34) on 4 to 5 weeks old Balb/c mice (n=42).
Results: According to the expression of Glycophorin-A (Ter119) and CD45R the MHC-I- compartment consists of four populations. Erythroid committed cells are the most represented, being Ter119+/CD45- in the vast majority (86.0±4.43%) and TER119+/CD45+ in only 0.2±0.13%. The two remaining MHC-I- populations are: Ter119-/CD45R+ (11.6±2.96%) and Ter119-/CD45R- (2.0±2.06%). Stem cells markers were expressed exclusively by MHC-I-/ Ter119-/CD45R+ cells, being cKit the most represented stem cell associated antigen. Mouse BDHSCs (MHC1-/Thy1+) are a rare subset (0.02%) of hematopoietic (CD45R+) cells and less represented than rat BDHSCs. MHC-I-/Ter119-/CD45- cells correspond to a fraction of MAPCs which are obtained by immunomagnetic selection of Ter119-/CD45- bone marrow cells. MAPCs have so far only been characterized in vitro where they appear to be all MHC-I-. In vivo they are composed of a mixture of MHC-I- (30%) and MHC-I+ cells and do not express any of the stem cell markers tested.
Conclusions: The presented analyses suggest that: 1) Mice BDHSCs and MAPCs are two phenotypically distinct populations; 2) MAPCs may derive from the clonal expansion of the MHC-I-/Ter119-/CD45- fraction; 3) Down-regulation of MHC-I is the only homology between BDHSC and MAPCs suggesting that selection of MHC-I- cells might represent a more efficient strategy to enrich for bone marrow derived stem cells with liver developmental potential.