C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation

Chan Suh Hyung, John Gooya, Katie Renn, Alan D. Friedman, Peter F. Johnson, Jonathan R. Keller

Research output: Contribution to journalArticlepeer-review

Abstract

C/EBPα is an essential transcription factor required for myeloid differentiation. While C/EBPα 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/EBPα-/- fetal liver (FL). Also, enforced expression of C/EBPα 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/EBPα 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/EBPα functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors.

Original languageEnglish (US)
Pages (from-to)4308-4316
Number of pages9
JournalBlood
Volume107
Issue number11
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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