Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning.
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 def...
| Publicado en: | Journal of Clinical Investigation Vol. 122; no. 10; pp. 3705 - 3718 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Society for Clinical Investigation
Oct2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104383479&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104383479 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00219738 0YX jtl: Journal of Clinical Investigation issn: 00219738 maglogo: N pubinfo: dt: Oct2012 vid: 122 iid: 10 pid: 11983 pub: American Society for Clinical Investigation place: Ann Arbor, Michigan artinfo: ui: 104383479 NLM22996665 2011754425 10.1172/JCI61619 NLM22996665 PMC3461906 104383479 ppf: 3705 ppct: 13 formats: tig: atl: Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. aug: au: Lim KC Hosoya T Brandt W Ku CJ Hosoya-Ohmura S Camper SA Yamamoto M Engel JD Lim, Kim-Chew Hosoya, Tomonori Brandt, William Ku, Chia-Jui Hosoya-Ohmura, Sakie Camper, Sally A Yamamoto, Masayuki Engel, James Douglas affil: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA sug: subj: Anemia Genetics Hematopoiesis Hemorrhage Lymphatic System Perinatal Death Proteins Physiology Anemia Embryology Animal Studies Cell Division Cell Physiology Colony-Forming Units Assay Female Genes Hematopoietic Stem Cells Pathology Hemorrhage Embryology Immunity Immunophenotyping Liver Embryology Lymphatic System Pathology Mice Pregnancy Protein Deficiency Tamoxifen Pharmacodynamics Female ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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