Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha
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, 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
Abstract
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.
Source: PubMed