NDLI: Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning

Content Provider	PubMed Central
Author	Lim, Kim-chew Hosoya, Tomonori Brandt, William Ku, Chia-jui Hosoya-ohmura, Sakie Camper, Sally A. Yamamoto, Masayuki Engel, James Douglas
Copyright Year	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 Gata2 VE enhancer (Gata2 VECre) and utilized it to temporally direct tissue-specific conditional loss of Gata2. Here, we report that Gata2 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 Gata2 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 Gata2 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.
Related Links	http://dx.doi.org/10.1172/jci61619
Ending Page	3717
Page Count	13
Starting Page	3705
File Format	PDF
ISSN	00219738
e-ISSN	15588238
Journal	The Journal of Clinical Investigation
Issue Number	10
Volume Number	122
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2012-10-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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