Distinct and regulated expression of Notch receptors in hematopoietic lineages and during myeloid differentiation

Hematopoietic development is a delicate balance of cell fate decisions in m ultipotent cells between self-renewal and differentiation. In multiple deve lopmental systems, the Notch receptors are important factors regulating the se processes. Hematopoietic progenitor cells have been shown to express Not ch1, and studies with an activated intracellular form has revealed a functi onal role. To assess the function of other Notch members in hematopoiesis, we investigated the expression pattern of Notch1, Notch2, and Notch3 in hem atopoietic lineages at the level of RNA and protein. We demonstrate that No tch1 and Notch2 are expressed in multiple lineages, and that Notch1 in part icular appears to be regulated during myeloid differentiation. Notch1 was u p-regulated and expressed at high levels in adherent macrophages. Mast cell s expressed only low levels of Notch1 mRNA whereas Notch2 mRNA was highly e xpressed. In addition we could detect Notch3 mRNA and protein in cell lines representing mast cell progenitors. These expression patterns imply that t he different Notch genes may have very distinct functions during hematopoie sis, and that Notch3 could be a specific regulator of mast cell development . The finding that Notch1 was up-regulated in the adherent cells developing from a multipotent progenitor cell line suggests that this protein may pos ses dual functions in hematopoiesis, i.e. at the stage of cell fate decisio n, and at the maturation stage of monocytes when adhesion to the specific m icroenvironment is accomplished.