Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning
Identifieur interne : 004419 ( Main/Curation ); précédent : 004418; suivant : 004420Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning
Auteurs : Kim-Chew Lim ; Tomonori Hosoya ; William Brandt ; Chia-Jui Ku ; Sakie Hosoya-Ohmura ; Sally A. Camper [États-Unis] ; Masayuki Yamamoto [Japon] ; James Douglas EngelSource :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2012.
Abstract
The transcription factor GATA-2 plays vital roles in quite diverse developmental programs, including hematopoietic stem cell (HSC) survival and proliferation. We previously identified a vascular endothelial (VE) enhancer that regulates GATA-2 activity in pan-endothelial cells. To more thoroughly define the in vivo regulatory properties of this enhancer, we generated a tamoxifen-inducible Cre transgenic mouse line using the
Url:
DOI: 10.1172/JCI61619
PubMed: 22996665
PubMed Central: 3461906
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PMC:3461906Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The transcription factor GATA-2 plays vital roles in quite diverse developmental programs, including hematopoietic stem cell (HSC) survival and proliferation. We previously identified a vascular endothelial (VE) enhancer that regulates GATA-2 activity in pan-endothelial cells. To more thoroughly define the in vivo regulatory properties of this enhancer, we generated a tamoxifen-inducible Cre transgenic mouse line using the <italic>Gata2</italic>
VE enhancer (<italic>Gata2</italic>
VECre) and utilized it to temporally direct tissue-specific conditional loss of <italic>Gata2</italic>
. Here, we report that <italic>Gata2</italic>
VECre–mediated loss of GATA-2 led to anemia, hemorrhage, and eventual death in edematous embryos. We further determined that the etiology of anemia in conditional <italic>Gata2</italic>
mutant embryos involved HSC loss in the fetal liver, as demonstrated by in vitro colony-forming and immunophenotypic as well as in vivo long-term competitive repopulation experiments. We further documented that the edema and hemorrhage in conditional <italic>Gata2</italic>
mutant embryos were due to defective lymphatic development. Thus, we unexpectedly discovered that in addition to its contribution to endothelial cell development, the VE enhancer also regulates GATA-2 expression in definitive fetal liver and adult BM HSCs, and that GATA-2 function is required for proper lymphatic vascular development during embryogenesis.
</p>
</div>
</front>
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