Runx1, c-Myb, and C/EBPalpha couple differentiation to proliferation or growth arrest during hematopoiesis

Abstract

Immature hematopoietic precursors proliferate as they differentiate, whereas terminal differentiation is associated with cell cycle arrest. Stem cell lineage commitment and subseqent maturation is regulated predominantly by transcription factors. Runx1 and c-Myb act in early stage hematopoietic cells to both stimulate proliferation and differentiation, whereas C/EBPalpha, and perhaps other C/EBP family members, block progression from G1 to S and induce terminal maturation. Coupling of differentiation to either proliferation or growth arrest by transcription factors is likely an important regulatory mechanism in multiple developmental systems.