Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha.
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.
Zhang
Pu
P
Harvard Institutes of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Iwasaki-Arai
Junko
J
Iwasaki
Hiromi
H
Fenyus
Maris L
ML
Dayaram
Tajhal
T
Owens
Bronwyn M
BM
Shigematsu
Hirokazu
H
Levantini
Elena
E
Huettner
Claudia S
CS
Lekstrom-Himes
Julie A
JA
Akashi
Koichi
K
Tenen
Daniel G
DG
D000375:Aging / Q000502:physiology; D000818:Animals; D001772:Blood Cell Count; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D005333:Fetus / Q000378:metabolism; D017353:Gene Deletion; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D022763:CCAAT-Enhancer-Binding Protein-alpha