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The zinc finger transcription factor GATA-2 plays a fundamental role in generating hematopoietic stem-cells in mammalian development. Less well defined is whether GATA-2 participates in adult stem-cell regulation, an issue we addressed using GATA-2 heterozygote mice that express reduced levels of GATA-2 in hematopoietic cells. While GATA-2+/- mice demonstrated decreases in some colony-forming progenitors, the most prominent changes were observed within the stem-cell compartment. Heterozygote bone marrow had a lower abundance of Lin(-)c-kit(+)Sca-1(+)CD34- cells and performed poorly in competitive transplantation and quantitative week-5 cobblestone area-forming cell (CAFC) assays. Furthermore, a stem-cell-enriched population from GATA1+/- marrow was more quiescent and exhibited a greater frequency of apoptotic cells associated with decreased expression of the anti-apoptotic gene Bcl-xL. Yet the self-renewal potential of the +/- stem-cell compartment, as judged by serial transplantations, was unchanged. These data indicate compromised primitive cell proliferation and survival in the setting of a lower GATA-2 gene dose without a change in the differentiation or self-renewal capacity of the stem-cells that remain. Thus, GATA-2 dose regulates adult stem-cell homeostasis by affecting select aspects of stem cell function.

Original publication

DOI

10.1182/blood-2004-08-2989

Type

Journal article

Journal

Blood

Publication Date

15/07/2005

Volume

106

Pages

477 - 484

Keywords

Animals, Apoptosis, Cell Cycle, Cells, Cultured, DNA-Binding Proteins, Female, GATA2 Transcription Factor, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Heterozygote, Homeostasis, Male, Mice, Mice, Knockout, RNA, Messenger, Transcription Factors