Thrombopoietin controls proliferation of embryonic multipotent hematopoietic progenitors

Abstract

Thrombopoietin (TPO) stimulation was reported to increase the number of multipotent hematopoietic progenitor (MPP) colonies in a methylcellose colony assay using cells from mouse embryos. Here, we investigated the expression of Mpl, the TPO receptor, in the cells from the yolk sac (YS) and the embryo proper (EP). MPPs in c-Kit(+) population in the mouse embryo expressed Mpl. Using liquid cultures, we found that MPPs from YS and EP proliferated in the presence of TPO and stem cell factor (SCF), whereas their numbers were maintained by TPO alone. In contrast, proliferation induced by TPO and SCF was not observed in MPPs of the bone marrow. Interestingly, examination of MPPs from the fetal liver indicated that their proliferative activity was intermediate between that of early embryonic and adult MPPs. These data suggest that early embryonic MPPs switch to adult MPPs in the embryo. Furthermore, the proliferation of early embryonic MPPs was suppressed by AG490, a Janus kinase2 (JAK2) inhibitor; and TPO could be replaced by constitutively active signal transducer and activator of transcription 5 (STAT5) for the proliferation. Thus, JAK2 and STAT5 mediate at least a part of the proliferative signal in early embryonic MPPs.