Cytokines & Cells Online Pathfinder Encyclopaedia
|
Horst Ibelgaufts' COPE:
Cytokines & Cells Online Pathfinder Encyclopaedia |
 |
 |
 |
 |
 |
 |
 |
| COPE Homepage | Previous entry: Hem-2 |
Next entry: hemangiogenesis |
Random entry: Semaphorin 5 |
These cells are primitive precursor cells of mesodermal origin that have the capacity of differentiating into either hematopoietic cells (see: hemocytoblasts) or vascular endothelial cells (Sabin, 1920; Wagner, 1980; Schatteman, 2004) (see also: hematopoiesis, angiogenesis). They have been found in the aorta-gonad-mesonephros region (AGM) of a developing embryo. Precursors with phenotypic and functional characteristics of embryonic hemangioblasts are also present in human adult bone marrow (Kocher et al, 2001).
The existence of hemangioblasts was first suggested by morphological studies of yolk sac development, specifically the close developmental association of hematopoietic and endothelial lineages within the blood islands (Pardanaud et al, 1989; Sabin, 1920; Murray, 1932; Wagner, 1980). In vitro culture studies of murine embryonic stem cells derived from embryoid bodies have led to the identification of bipotent cells that persist for a short period of time preceding the onset of hematopoiesis and vasculogenesis. These cells have been termed BL-CFC (blast colony-forming cells) and most likely represent the in vitro equivalent of hemangioblasts (Choi et al, 1998). Blast-like cells express a number of genes common to hematopoietic and endothelial lineages, including SCL (Tal-1), CD34, and the VEGF receptor, flk-1 (Kennedy et al, 1997). Hemangioblasts may give rise to yolk sac hematopoietic stem cells (YS-HSC), which have a greater reproductive capability than hematopoietic stem cells obtained from fetal liver, umbilical cord blood or adult bone marrow (Auerbach et al, 1996). Kubo et al (2005) have reported that the homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation (2005).
Hemangioblasts cannot be identified morphologically but they share some features with hematopoietic stem cells, including expression of CD34 (Asahara et al, 1994; Young et al, 1995; Fina et al, 1990), flk-1 (VEGF receptor-2, KDR; Kabrun et al, 1997; Yamaguchi et al, 1993; Millauer et al, 1993; Asahara et al, 1994) and various transcription factors such as LMO2 (Shivdasani and Orkin, 1996), GATA-2 (Shivdasani and Orkin, 1996), SCL (Tal-1) (Kalianpur et al, 1994), some of which are required for primitive hematopoiesis and others for definite hematopoiesis. Hemangioblasts found in the AGM region of mouse embryos have been identified also by their expression of a specific surface marker, PCLP1 [podocalyxin-like protein 1] (Hara et al, 1999).
Guo et al (2003) have isolated fetal mouse bone marrow cells that express the flk-1 receptor and do not express CD31 (PECAM-1), CD45, GlyA, and CD34. They have demonstrated that these cells have characteristics of hemangioblasts, which, under appropriate conditions, differentiate into endothelial and hematopoietic cells.
Shaw et al (2004) have reported that approximately 4x10**-3 % of bone marrow cells express TIE-2, Sca-1, CD31, and CD45, and also function as both bone marrow-derived endothelial progenitor cells and primitive hematopoietic stem cells, with approximately 3500 of these cells being sufficient to radioprotect lethally irradiated mice.
Falcoon et al (2000) have reported that these cells express the receptor tyrosine kinase, flk-1, one of the receptors for VEGF, and that bFGF is critical for the proliferation of hemangioblasts. Miyagi et al (2002) have used embryonic stem cells to obtain cells that express Flk-1 and the SCF receptor. These cells are capable of reconstituting hematopoiesis in vivo in SCID mice.
Pelosi et al (2002) have identified postnatal hemangioblasts in a CD34(+) flk-1(+) cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity, being capable to form colonies in a colony formation assay that are hemato-endothelial colonies. These colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or hemato-endothelial colonies, depending on the specific culture conditions.
Minko et al (2003) have reported that expression of SCL and LMO2 is restricted to presumptive hemangioblasts and that LMO2 is upregulated in blood island angioblasts, thus appearing as one of the earliest markers for endothelial cell commitment. Gering et al (1998) have reported that forced expression of SCL causes an expansion of the hemangioblast population. The lack of expression of SCL in knock-out mice causes early embryonic death due to a complete failure of both primitive hematopoiesis (yolk sac) and definitive hematopoiesis (intra-embryonic) (Shivdasani et al, 1995). GATA-2 gene disruption in knock-out mice is also embryonic lethal. GATA-2 mainly affects the development of definitive blood cells (Tsai et al, 1994).
The study of knock-out mice lacking expression of flk-1 (Shalaby et al, 1995, 1997) or VEGF (Carmeliet et al, 1996; Ferrara et al, 1996) has demonstrated a severe impairment in the development of both the hematopoietic cell and endothelial cell lineages in these mice. Cells from flk-1 negative mice are also unable to colonize the developing yolk sac region of these embryos (Shalaby et al, 1997). Chung et al (2002) have used embryonic stem cells to carry out a lineage analysis of hemangioblasts with respect to the expression of flk-1 and the transcription factor Tal-1. Hemangioblasts give rise to hematopoietic and endothelial cells in discrete steps. The developing embryoid body contains cells that are flk-1(+) CD4(-). These cells begin to express Tal-1 and develop into flk-1(+) CD4(+) cells. Some flk-1(+) CD4(-) cells remain Tal-1(-). flk-1(+) CD4(+) cells then downregulate expression of flk-1 to generate flk-1(-) CD4(+) cells. Hematopoietic progenitors are enriched within flk-1(+) CD4(+) and flk-1(-) CD4(+) cells. Endothelial cells develop from flk-1(+) CD4(+) and flk-1(+) CD4(-) cell populations. Endoh et al (2002) have used Tal-1(-) embryonic stem cells in which Tal-1 expression can be switched on. Primitive hematopoiesis and definitive hematopoiesis can be restored if Tal-1 expression is reactivated between days 2-4 after initiation of differentiation whereas reactivation of Tal-1 expression at later phases is ineffective. Tal-1 reactivation has to occur prior to VE-cadherin expression for the rescue of definite hematopoiesis. Park et al (2004) have reported that BMP4 is required for the generation of flk-1(+) Tal-1(+) cells and that VEGF is necessary for the expansion and differentiation of Tal-1(+) hematopoietic progenitors. flk-1(-) embryonic stem cells respond to BMP4 and generate TER-119(+) and CD31(+) cells, but fail to expand in response to VEGF. VEGF mediated expansion of hematopoietic and endothelial cell progenitors is inhibited by TGF-beta-1, and is augmented by activin A.
Perlingeiro et al (2003) have demonstrated that, apart from VEGF and SCF, which act as growth factors for hemangioblasts, Thrombopoietin together with its receptor, mpl, also influences the formation of hemangioblasts in a colony formation assay. Oncostatin M enhances the development of both hematopoietic and endothelial cells by possibly stimulating hemangioblasts (Miyajima et al, 2000).
Minehata et al (2002) have reported that M-CSF modulates the development of hematopoiesis by stimulating the differentiation of PCLP1(+) CD45(-) cells to endothelial cells in the AGM region.
Haigh et al (2004) have reported that the cytoplasmic tyrosine kinase Fes together with flk-1 modulate hemangioblast differentiation into the endothelium.
Wang et al (2004) have reported that the differentiation of hemangioblasts and other cell types, as well as vascular differentiation is impaired in embryonic stem cells lacking expression of the Ephrin receptor, EphB4.
Chan et al (2003) have pointed out a critical role of Shp-2 tyrosine phosphatase in the differentiation of ES cells to mesoderm and to hemangioblasts that maintains a proper balance of differentiation, pluripotency, and apoptosis of ES cells.
For other entries pertaining to hematopoiesis see also the Hematology Dictionary section of this encyclopedia.
For related information see also: Cell types, Cell lines in Cytokine Research, Cell culture.
LAST MODIFIED: September 2006
See REFERENCES for entry hemangioblasts
| SUPPORT COPE | Intro | Subdictionaries | New Entries | Contribute data | COPE Credentials |
| # | A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |
|
Space for your TEXTLINK ADVERTISEMENTS. Please Inquire
|
 |
 |
 |
 |
 |
 |
 |
supports the COPE bioinformatics project with an unrestricted educational grant |
Created, developed, and maintained by Prof Dr H Ibelgaufts
|
| Access to COPE is free only for academic institutions and non-profit organizations. OTHER USERS: must contact COPE and pay a site licence fee. Non-payment of the site licence fee is a serious breach of COPE's binding Usage Agreement. If you do not wish to be bound by this agreement, do not use COPE |
| COPE is not in the public domain! The commercial use of COPE contents is not allowed. Download of complete offline-readable copies and the use of automatic extraction methods are prohibited! Usage Agreement, Disclaimer, Copyright Notice | All rights reserved by H Ibelgaufts | Privacy Statement U L T R A P O S S E N E M O O B L I G A T U R |