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

Pu Zhang, Junko Iwasaki-Arai, Hiromi Iwasaki, Maris L. Fenyus, Tajhal Dayaram, Bronwyn M. Owens, Hirokazu Shigematsu, Elena Levantini, Claudia S. Huettner, Julie A. Lekstrom-Himes, Koichi Akashi, Daniel G. Tenen

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Abstract

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

Original languageEnglish
Pages (from-to)853-863
Number of pages11
JournalImmunity
Volume21
Issue number6
DOIs
Publication statusPublished - Dec 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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  • Cite this

    Zhang, P., Iwasaki-Arai, J., Iwasaki, H., Fenyus, M. L., Dayaram, T., Owens, B. M., Shigematsu, H., Levantini, E., Huettner, C. S., Lekstrom-Himes, J. A., Akashi, K., & Tenen, D. G. (2004). Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity, 21(6), 853-863. https://doi.org/10.1016/j.immuni.2004.11.006