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.
Suh
Hyung Chan
HC
Basic Research Program, Science Applications International Corporation-Frederick, National Cancer Institute at Frederick, MD 20702-1201, USA.
Gooya
John
J
Renn
Katie
K
Friedman
Alan D
AD
Johnson
Peter F
PF
Keller
Jonathan R
JR
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