SOX7 regulates the expression of VE-cadherin in the haemogenic endothelium at the onset of haematopoietic development

被引:74
作者
Costa, Guilherme [1 ,3 ]
Mazan, Andrzej [1 ]
Gandillet, Arnaud [4 ]
Pearson, Stella [1 ]
Lacaud, Georges [2 ]
Kouskoff, Valerie [1 ]
机构
[1] Univ Manchester, Canc Res UK Stem Cell Res Grp, Manchester M20 4BX, Lancs, England
[2] Univ Manchester, Paterson Inst Canc Res, Stem Cell Biol Grp, Manchester M20 4BX, Lancs, England
[3] Univ Porto, Grad Program Areas Basic & Appl Biol GABBA, P-4099002 Oporto, Portugal
[4] London Res Inst, Canc Res UK Haematopoiet Stem Cell Grp, London WC2A 3LY, England
来源
DEVELOPMENT | 2012年 / 139卷 / 09期
关键词
Haemangioblast; Haematopoiesis; Haemogenic endothelium; SOX7; VE-cadherin (cadherin 5); Mouse; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; REDUNDANT ROLES; GENE-EXPRESSION; IN-VITRO; AORTIC ENDOTHELIUM; ADHESION MOLECULE; LENTIVIRUS VECTOR; COMMON PRECURSOR; LINEAGE ANALYSIS;
D O I
10.1242/dev.071282
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
At early stages of vertebrate ontogeny, blood and endothelial cells develop from a common mesodermal progenitor, the haemangioblast. Upon haematopoietic commitment, the haemangioblast generates blood precursors through populations of endothelial cells with haemogenic properties. Although several transcription factors have been implicated in haemangioblast differentiation, the precise mechanisms governing cell fate decisions towards the generation of haemogenic endothelium precursors remain largely unknown. Under defined conditions, embryonic stem (ES) cells can be differentiated into haemangioblast-like progenitors that faithfully recapitulate early embryonic haematopoiesis. Here, we made use of mouse ES cells as a model system to understand the role of SOX7, a member of a large family of transcription factors involved in a wide range of developmental processes. During haemangioblast differentiation, SOX7 is expressed in haemogenic endothelium cells and is downregulated in nascent blood precursors. Gain-of-function assays revealed that the enforced expression of Sox7 in haemangioblast-derived blast colonies blocks further differentiation and sustains the expression of endothelial markers. Thus, to explore the transcriptional activity of SOX7, we focused on the endothelial-specific adhesion molecule VE-cadherin. Similar to SOX7, VE-cadherin is expressed in haemogenic endothelium and is downregulated during blood cell formation. We show that SOX7 binds and activates the promoter of VE-cadherin, demonstrating that this gene is a novel downstream transcriptional target of SOX7. Altogether, our findings suggest that SOX7 is involved in the transcriptional regulation of genes expressed in the haemogenic endothelium and provide new clues to decipher the molecular pathways that drive early embryonic haematopoiesis.
引用
收藏
页码:1587 / 1598
页数:12
相关论文
共 65 条
[1]   Haematopoietic stem cells derive directly from aortic endothelium during development [J].
Bertrand, Julien Y. ;
Chi, Neil C. ;
Santoso, Buyung ;
Teng, Shutian ;
Stainier, Didier Y. R. ;
Traver, David .
NATURE, 2010, 464 (7285) :108-U120
[2]   Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin [J].
Birdsey, Graeme M. ;
Dryden, Nicola H. ;
Amsellem, Valerie ;
Gebhardt, Frank ;
Sahnan, Kapil ;
Haskard, Dorian O. ;
Dejana, Elisabetta ;
Mason, Justin C. ;
Randi, Anna M. .
BLOOD, 2008, 111 (07) :3498-3506
[3]   In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium [J].
Boisset, Jean-Charles ;
van Cappellen, Wiggert ;
Andrieu-Soler, Charlotte ;
Galjart, Niels ;
Dzierzak, Elaine ;
Robin, Catherine .
NATURE, 2010, 464 (7285) :116-U131
[4]   Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators [J].
Bowles, J ;
Schepers, G ;
Koopman, P .
DEVELOPMENTAL BIOLOGY, 2000, 227 (02) :239-255
[5]   Molecular cloning and expression of murine vascular endothelial cadherin in early stage development of cardiovascular system [J].
Breier, G ;
Breviario, F ;
Caveda, L ;
Berthier, R ;
Schnurch, H ;
Gotsch, U ;
Vestweber, D ;
Risau, W ;
Dejana, E .
BLOOD, 1996, 87 (02) :630-641
[6]   JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update [J].
Bryne, Jan Christian ;
Valen, Eivind ;
Tang, Man-Hung Eric ;
Marstrand, Troels ;
Winther, Ole ;
da Piedade, Isabelle ;
Krogh, Anders ;
Lenhard, Boris ;
Sandelin, Albin .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D102-D106
[7]   Sox18 and Sox7 play redundant roles in vascular development [J].
Cermenati, Solei ;
Moleri, Silvia ;
Cimbro, Simona ;
Corti, Paola ;
Del Giacco, Luca ;
Amodeo, Roberta ;
Dejana, Elisabetta ;
Koopman, Peter ;
Cotelli, Franco ;
Beltrame, Monica .
BLOOD, 2008, 111 (05) :2657-2666
[8]   Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter [J].
Chen, Michael J. ;
Yokomizo, Tomomasa ;
Zeigler, Brandon M. ;
Dzierzak, Elaine ;
Speck, Nancy A. .
NATURE, 2009, 457 (7231) :887-891
[9]  
Choi K, 1998, DEVELOPMENT, V125, P725
[10]   Lineage analysis of the hemangioblast as defined by FLK1 and SCL expression [J].
Chung, YS ;
Zhang, WJ ;
Arentson, E ;
Kingsley, PD ;
Palis, J ;
Choi, K .
DEVELOPMENT, 2002, 129 (23) :5511-5520