title: Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha.
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.
authors.affiliation: Harvard Institutes of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.forename: Junko
authors.initials: J
authors.lastname: Iwasaki-Arai
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Maris L
authors.initials: ML
authors.lastname: Fenyus
authors.forename: Tajhal
authors.initials: T
authors.lastname: Dayaram
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: Owens
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Huettner
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lekstrom-Himes
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: 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
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha