The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage

被引:479
作者
Lancrin, Christophe [1 ]
Sroczynska, Patrycja [1 ]
Stephenson, Catherine [1 ]
Allen, Terry [2 ]
Kouskoff, Valerie [3 ]
Lacaud, Georges [1 ]
机构
[1] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Stem Cell Biol Grp, Manchester M20 4BX, Lancs, England
[2] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Struct Cell Biol Grp, Manchester M20 4BX, Lancs, England
[3] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Stem Cell Haematopoiesis Grp, Manchester M20 4BX, Lancs, England
关键词
EMBRYONIC STEM-CELL; DEFINITIVE HEMATOPOIESIS; MOUSE EMBRYO; YOLK-SAC; COMMON PRECURSOR; TYROSINE KINASE; IN-VITRO; EXPRESSION; HEMANGIOBLAST; COMMITMENT;
D O I
10.1038/nature07679
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
It has been proposed that during embryonic development haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast(1,2). A conflicting theory instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell that has haematopoietic potential ( that is, a haemogenic endothelium) (3-5). Support for the haemangioblast concept was initially provided by the identification during mouse embryonic stem cell differentiation of a clonal precursor, the blast colony- forming cell (BL-CFC), which gives rise to blast colonies with both endothelial and haematopoietic components(6,7). Although recent studies have now provided evidence for the presence of this bipotential precursor in vivo(8,9), the precise mechanism for generation of haematopoietic cells from the haemangioblast still remains completely unknown. Here we demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. The cell population containing the haemogenic endothelium is transiently generated during BL-CFC development. This cell population is also present in gastrulating mouse embryos and generates haematopoietic cells on further culture. At the molecular level, we demonstrate that the transcription factor Tal1 ( also known as Scl; ref. 10) is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1 ( also known as AML1; ref. 11) is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge the two a priori conflicting theories on the origin of haematopoietic development into a single linear developmental process.
引用
收藏
页码:892 / 895
页数:4
相关论文
共 30 条
[1]   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
[2]  
Choi K, 1998, DEVELOPMENT, V125, P725
[3]   SCL/Tal-1 is essential for hernatopoietic commitment of the hemangioblast but not for its development [J].
D'Souza, SL ;
Elefanty, AG ;
Keller, G .
BLOOD, 2005, 105 (10) :3862-3870
[4]  
DUMONT DJ, 1992, ONCOGENE, V7, P1471
[5]  
Faloon P, 2000, DEVELOPMENT, V127, P1931
[6]   Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation [J].
Fehling, HJ ;
Lacaud, G ;
Kubo, A ;
Kennedy, M ;
Robertson, S ;
Keller, G ;
Kouskoff, V .
DEVELOPMENT, 2003, 130 (17) :4217-4227
[7]   CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo [J].
Ferkowicz, MJ ;
Starr, M ;
Xie, XD ;
Li, WM ;
Johnson, SA ;
Shelley, WC ;
Morrison, PR ;
Yoder, MC .
DEVELOPMENT, 2003, 130 (18) :4393-4403
[8]   ROLE OF THE FLT-1 RECEPTOR TYROSINE KINASE IN REGULATING THE ASSEMBLY OF VASCULAR ENDOTHELIUM [J].
FONG, GH ;
ROSSANT, J ;
GERTSENSTEIN, M ;
BREITMAN, ML .
NATURE, 1995, 376 (6535) :66-70
[9]   NOVEL MOUSE ENDOTHELIAL-CELL SURFACE MARKER IS SUPPRESSED DURING DIFFERENTIATION OF THE BLOOD-BRAIN-BARRIER [J].
HALLMANN, R ;
MAYER, DN ;
BERG, EL ;
BROERMANN, R ;
BUTCHER, EC .
DEVELOPMENTAL DYNAMICS, 1995, 202 (04) :325-332
[10]   Hemogenic and nonhemogenic endothelium can be distinguished by the activity of fetal liver kinase (Flk)-1 promoter/enhancer during mouse embryogenesis [J].
Hirai, H ;
Ogawa, M ;
Suzuki, N ;
Yamamoto, M ;
Breier, G ;
Mazda, O ;
Imanishi, J ;
Nishikawa, S .
BLOOD, 2003, 101 (03) :886-893