SELF-RENEWAL AND DIFFERENTIATION OF NORMAL AVIAN ERYTHROID PROGENITORCELLS - REGULATORY ROLES OF THE TGF-ALPHA C-ERBB AND SCF/C-KIT RECEPTORS/

The c-kit proto-oncogene product is a major regulator of early hematop oiesis in mice. We show here that the avian c-Kit protein, together wi th the c-erbB proto-oncogene product, regulates self-renewal and diffe rentiation in two types of normal chick erythroid progenitors. A relat ively frequent progenitor expressing only c-Kit transiently proliferat ed in response to avian c-Kit ligand (stem cell factor [SCF]). A secon d, rare progenitor coexpressed c-Kit and c-ErbB and was induced to lon g-term self-renewal by SCF or transforming growth factor alpha(TGFalph a), a c-ErbB ligand. In the absence of SFC or TGFalpha, both progenito rs underwent erythropoietin (Epo)-dependent terminal differentiation w ith indistinguishable kinetics. Interestingly, Epo induced differentia tion in the SCF progenitors even when SCF was present. In contrast, th e c-ErbB-expressing, TGFalpha-induced progenitors continued to self-re new when treated with Epo plus the growth factors SCF, TGFalpha, or bo th. Expression of c-ErbB thus may be a dominant determinant for the su stained self-renewal of committed erythroid progenitors.