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The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization

(2011) BLOOD. 117(21). p.5620-5630
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Abstract
Zeb2 (Sip1/Zfhx1b) is a member of the zinc-finger E-box- inding (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 beta 1 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.
Keywords
CD34(+) CELLS, IN-VIVO, TRANSGENIC MICE, CHEMOKINE SDF-1, TARGETED DISRUPTION, STEM-CELLS, FETAL LIVER HEMATOPOIESIS, EPITHELIAL-MESENCHYMAL TRANSITION, SMAD-INTERACTING PROTEIN-1, MOWAT-WILSON-SYNDROME

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Chicago
Goossens, Steven, Viktor Janzen, Sona Bartunkova, Tomomasa Yokomizo, Benjamin Drogat, Mihaela Crisan, Katharina Haigh, et al. 2011. “The EMT Regulator Zeb2/Sip1 Is Essential for Murine Embryonic Hematopoietic Stem/progenitor Cell Differentiation and Mobilization.” Blood 117 (21): 5620–5630.
APA
Goossens, S., Janzen, V., Bartunkova, S., Yokomizo, T., Drogat, B., Crisan, M., Haigh, K., et al. (2011). The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization. BLOOD, 117(21), 5620–5630.
Vancouver
1.
Goossens S, Janzen V, Bartunkova S, Yokomizo T, Drogat B, Crisan M, et al. The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization. BLOOD. 2011;117(21):5620–30.
MLA
Goossens, Steven, Viktor Janzen, Sona Bartunkova, et al. “The EMT Regulator Zeb2/Sip1 Is Essential for Murine Embryonic Hematopoietic Stem/progenitor Cell Differentiation and Mobilization.” BLOOD 117.21 (2011): 5620–5630. Print.
@article{1260998,
  abstract     = {Zeb2 (Sip1/Zfhx1b) is a member of the zinc-finger E-box- inding (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 beta 1 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.},
  author       = {Goossens, Steven and Janzen, Viktor and Bartunkova, Sona and Yokomizo, Tomomasa and Drogat, Benjamin and Crisan, Mihaela and Haigh, Katharina and Seuntjens, Eve and Umans, Lieve and Riedt, Tamara and Bogaert, Pieter and Haenebalcke, Lieven and Berx, Geert and Dzierzak, Elaine and Huylebroeck, Danny and Haigh, Jody},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keyword      = {CD34(+) CELLS,IN-VIVO,TRANSGENIC MICE,CHEMOKINE SDF-1,TARGETED DISRUPTION,STEM-CELLS,FETAL LIVER HEMATOPOIESIS,EPITHELIAL-MESENCHYMAL TRANSITION,SMAD-INTERACTING PROTEIN-1,MOWAT-WILSON-SYNDROME},
  language     = {eng},
  number       = {21},
  pages        = {5620--5630},
  title        = {The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization},
  url          = {http://dx.doi.org/10.1182/blood-2010-08-300236},
  volume       = {117},
  year         = {2011},
}

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