C/EBPalpha determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation.
C/EBPalpha is an essential transcription factor required for myeloid differentiation. While C/EBPalpha can act as a cell fate switch to promote granulocyte differentiation in bipotential granulocyte-macrophage progenitors (GMPs), its role in regulating cell fate decisions in more primitive progenitors is not known. We found increased numbers of erythroid progenitors and erythroid cells in C/EBPalpha(-/-) fetal liver (FL). Also, enforced expression of C/EBPalpha in hematopoietic stem cells resulted in a loss of erythroid progenitors and an increase in myeloid cells by inhibition of erythroid development and inducing myeloid differentiation. Conditional expression of C/EBPalpha in murine erythroleukemia (MEL) cells induced myeloid-specific genes, while inhibiting erythroid-specific gene expression including erythropoietin receptor (EpoR), which suggests a novel mechanism to determine hematopoietic cell fate. Thus, C/EBPalpha functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors.
Basic Research Program, Science Applications International Corporation-Frederick, National Cancer Institute at Frederick, MD 20702-1201, USA.
Hyung Chan
HC
Suh
John
J
Gooya
Katie
K
Renn
Alan D
AD
Friedman
Peter F
PF
Johnson
Jonathan R
JR
Keller
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology; D006410:Hematopoiesis; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology*; D022423:Myeloid Cells / Q000166:cytology*; D017467:Receptors, Erythropoietin / Q000235:genetics; D014162:Transfection
D022763:CCAAT-Enhancer-Binding Protein-alpha; D017467:Receptors, Erythropoietin