Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 5620-30 |
Number of pages | 11 |
Journal | Blood |
Volume | 117 |
Issue number | 21 |
DOIs | |
Publication status | Published - 26 May 2011 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Cadherins
- Cell Differentiation
- Cell Movement
- Embryo, Mammalian
- Epithelial-Mesenchymal Transition
- Female
- Flow Cytometry
- Genes, Lethal
- Hematopoiesis
- Hematopoietic Stem Cells
- Homeodomain Proteins
- Integrases
- Male
- Mice
- Mice, Knockout
- Repressor Proteins
- Zinc Fingers