The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis
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 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.
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Metadata
- Authors
- Rodrigues, N. P.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-07-15
- Volume
- 106
- Issue
- 2
- Pages
- 477-484
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1971958267
- Cited by
- 297
- References
- 7
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- closed
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