| First Author | Rodrigues NP | Year | 2005 |
| Journal | Blood | Volume | 106 |
| Issue | 2 | Pages | 477-84 |
| PubMed ID | 15811962 | Mgi Jnum | J:107471 |
| Mgi Id | MGI:3621261 | Doi | 10.1182/blood-2004-08-2989 |
| Citation | Rodrigues NP, et al. (2005) Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis. Blood 106(2):477-84 |
| abstractText | 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. |
