The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization
| Autor: | Lieven Haenebalcke, Katharina Haigh, Mihaela Crisan, Danny Huylebroeck, Tomomasa Yokomizo, Steven Goossens, Geert Berx, Viktor Janzen, Elaine Dzierzak, Sonia Bartunkova, Jody J. Haigh, Lieve Umans, Pieter Bogaert, Eve Seuntjens, Benjamin Drogat, Tamara Riedt |
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| Přispěvatelé: | Cell biology |
| Rok vydání: | 2011 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition Immunology Biology Biochemistry CXCR4 Mice Cell Movement medicine Animals Progenitor cell Zinc Finger E-box Binding Homeobox 2 Homeodomain Proteins Mice Knockout Integrases Embryogenesis Embryo Cell Differentiation Zinc Fingers Cell Biology Hematology Cadherins Embryo Mammalian Flow Cytometry Hematopoietic Stem Cells Embryonic stem cell Cell biology Hematopoiesis Repressor Proteins Haematopoiesis medicine.anatomical_structure Tumor progression embryonic structures Female Genes Lethal Bone marrow |
| Zdroj: | Blood, 117(21), 5620-5630. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2010-08-300236 |
| Popis: | Zeb2 (Sip1/Zfhx1b) is a member of the zinc-finger E-box-binding (ZEB) family of transcriptional repressors previously demonstrated to regulate epithelial-to-mesenchymal transition (EMT) processes during embryogenesis and tumor progression. We found high Zeb2 mRNA expression levels in HSCs and hematopoietic progenitor cells (HPCs), and examined Zeb2 function in hematopoiesis through a conditional deletion approach using the Tie2-Cre and Vav-iCre recombination mouse lines. Detailed cellular analysis demonstrated that Zeb2 is dispensable for hematopoietic cluster and HSC formation in the aorta-gonadomesonephros region of the embryo, but is essential for normal HSC/HPC differentiation. In addition, Zeb2-deficient HSCs/HPCs fail to properly colonize the fetal liver and/or bone marrow and show enhanced adhesive properties associated with increased β1 integrin and Cxcr4 expression. Moreover, deletion of Zeb2 resulted in embryonic (Tie2-Cre) and perinatal (Vav-icre) lethality due to severe cephalic hemorrhaging and decreased levels of angiopoietin-1 and, subsequently, improper pericyte coverage of the cephalic vasculature. These results reveal essential roles for Zeb2 in embryonic hematopoiesis and are suggestive of a role for Zeb2 in hematopoietic-related pathologies in the adult. ispartof: Blood vol:117 issue:21 pages:5620-5630 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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