Self-renewal and differentiation of normal avian erythroid progenitor cells: 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 hematopoiesis in mice. We show here that the avian c-Kit protein, together with the c-erbB protooncogene product, regulates self-renewal and differentiation in two types of normal chick erythroid progenitors. A relatively frequent progenitor expressing only c-Kit transiently proliferated in response to avian c-Kit ligand (stem cell factor [SCF]). A second, rare progenitor coexpressed c-Kit and c-ErbB and was induced to long-term self-renewal by SCF or transforming growth factor alpha (TGF alpha), a c-ErbB ligand. In the absence of SFC or TGF alpha, both progenitors underwent erythropoietin (Epo)-dependent terminal differentiation with indistinguishable kinetics. Interestingly, Epo induced differentiation in the SCF progenitors even when SCF was present. In contrast, the c-ErbB-expressing, TGF alpha-induced progenitors continued to self-renew when treated with Epo plus the growth factors SCF, TGF alpha, or both. Expression of c-ErbB thus may be a dominant determinant for the sustained self-renewal of committed erythroid progenitors.
Hayman
M J
MJ
Department of Microbiology, State University of New York, Stony Brook 11794.
Meyer
S
S
Martin
F
F
Steinlein
P
P
Beug
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002645:Chickens / Q000097:blood / Q000254:growth & development; D066246:ErbB Receptors / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology* / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D013047:Specific Pathogen-Free Organisms; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit