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Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis

Rodrigues, Neil, Janzen, V., Forkert, R., Dombkowski, D. M., Boyd, A. S., Orkin, S. H., Enver, T., Vyas, P. and Scadden, D. 2005. Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis. Blood 106 (2) , pp. 477-484. 10.1182/blood-2004-08-2989

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Abstract

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 antiapoptotic 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 04 Jun 2017 06:40
URI: http://orca.cf.ac.uk/id/eprint/63475

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