par Goossens, Steven;Janzen, Viktor;Bartunkova, Sonia;Yokomizo, Tomomasa;Drogat, Benjamin ;Crisan, Mihaela;Haigh, Katharina;Seuntjens, Eve;Umans, Lieve;Riedt, Tamara;Bogaert, Pieter;Haenebalcke, Lieven;Berx, Geert;Dzierzak, Elaine;Huylebroeck, Danny;Haigh, Jody J
Référence Blood, 117, 21, page (5620-5630)
Publication Publié, 2011-05
Référence Blood, 117, 21, page (5620-5630)
Publication Publié, 2011-05
Article révisé par les pairs
Résumé : | 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. |