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

Steven Goossens UGent, Viktor Janzen, Sona Bartunkova UGent, Tomomasa Yokomizo, Benjamin Drogat UGent, Mihaela Crisan, Katharina Haigh UGent, Eve Seuntjens, Lieve Umans and Tamara Riedt, et al. (2011) BLOOD. 117(21). p.5620-5630
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
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
journal title
BLOOD
Blood
volume
117
issue
21
pages
5620 - 5630
Web of Science type
Article
Web of Science id
000291010500014
JCR category
HEMATOLOGY
JCR impact factor
9.898 (2011)
JCR rank
2/68 (2011)
JCR quartile
1 (2011)
ISSN
0006-4971
DOI
10.1182/blood-2010-08-300236
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1260998
handle
http://hdl.handle.net/1854/LU-1260998
date created
2011-06-14 10:53:09
date last changed
2012-06-26 14:32:20
@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},
}

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.