Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha

Immunity. 2004 Dec;21(6):853-63. doi: 10.1016/j.immuni.2004.11.006.


The transcription factor C/EBP alpha is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBP alpha blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBP alpha-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBP alpha-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBP alpha cooperates with other events in the development of leukemia. Therefore, C/EBP alpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology
  • Animals
  • Blood Cell Count
  • CCAAT-Enhancer-Binding Protein-alpha / deficiency*
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation*
  • Fetus / metabolism
  • Gene Deletion
  • Granulocytes / cytology
  • Granulocytes / metabolism
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Liver / cytology
  • Liver / metabolism
  • Mice
  • Mice, Knockout


  • CCAAT-Enhancer-Binding Protein-alpha