The embryonic origins of human haematopoiesis

Marshall, Caroline; Thrasher, Adrian J.

doi:10.1046/j.1365-2141.2001.02537.x

Cited by 77 publications

(48 citation statements)

References 79 publications

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“…However, because developmental stages of embryos within littermates have some variation (Downs and Davies, 1993), whereas activation of cre-ER driven under Runx-1 promoter by tamoxifen is simultaneous (Samokhvalov et al, 2007), further experiments are still needed regarding the existence and role of hemogenic endothelial cells as a shared progenitor in the endothelial and blood development pathways. These cells were first observed in experiments where blood cells were found to be generated from a subset of phenotypically differentiated endothelial cells on the wall of the embryonic aorta (Marshall and Thrasher, 2001;North et al, 1999;Tavian et al, 1999). The so-called hemogenic endothelial cells possessing hematopoietic potential are initially identified in the AGM region at around E10.5 (Jaffredo et al, 1998;North et al, 2002).…”

Section: -10 Daysmentioning

confidence: 99%

“…Moreover, it is well known that progenitors for endothelial and hematopoietic cells share common markers e.g. Flk1 (Shalaby et al, 1997), Scl (Jaffredo et al, 2005), lmo2 (Manaia et al, 2000), Tie1 (Marshall and Thrasher, 2001), Tie2 (Takakura et al, 1998), CD31 (GarciaPorrero et al, 1998), CD34 (Wood et al, 1997). However, no common gene expression or gene knockout or knockdown study can be used to delineate lineages; they only show the importance of the gene.…”

Section: Lineage Relationships Between Endothelial and Hematopoietic mentioning

confidence: 99%

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The origin and fate of yolk sac hematopoiesis: application of chimera analyses to developmental studies

Ueno

Weissman²

2010

Int. J. Dev. Biol.

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During mammalian development, as exemplified by mice, hematopoietic cells first appear in the yolk sac blood islands, then in the dorsal aorta of the aorta-gonad-mesonephros (AGM) region and the placenta, eventually seeding into liver, spleen and then bone marrow. The formation of hematopoietic stem cells from mesodermal precursors has finished by mid-fetal life. Once established, the hematopoietic system must supply blood cells to host circulation and tissues for the entire life of the animal. Easy access to hematopoietic cells has enabled a vast number of studies over the last several decades, and much is now understood about the different hematopoietic lineages, how they differentiate, and their derivation from immature progenitors. Yet to be elucidated are the following two intriguing questions: do yolk sac and AGM hematopoietic cells arise from a common precursor or from distinct precursor cells?; and what is the lineage relationship between blood and endothelial cells. In this review, we will survey the state of our current knowledge in these areas, and discuss the potential use of multicolor chimera analyses to elucidate unresolved questions.

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Section: -10 Daysmentioning

confidence: 99%

Section: Lineage Relationships Between Endothelial and Hematopoietic mentioning

confidence: 99%

The origin and fate of yolk sac hematopoiesis: application of chimera analyses to developmental studies

Ueno

Weissman²

2010

Int. J. Dev. Biol.

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“…Hematopoietic clusters have been examined in a variety of vertebrate embryos (Jaffredo et al, 2005) and characterized by immuno-and histochemical staining of transversal sections (Garcia-Porrero et al, 1995;Garcia-Porrero et al, 1998;Jaffredo et al, 1998;Marshall and Thrasher, 2001;North et al, 1999;North et al, 2002;Taoudi and Medvinsky, 2007;Tavian et al, 1996). A reconstruction of an immunostained 5-week human embryonic aorta made from 72 transverse sections with a thickness of 5 m each (one or two somite pairs in preumbilical region) shows 831 CD34 + clustered cells (Tavian et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos

2010

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SUMMARYHematopoietic cell clusters in the aorta of vertebrate embryos play a pivotal role in the formation of the adult blood system. Despite their importance, hematopoietic clusters have not been systematically quantitated or mapped because of technical limitations posed by the opaqueness of whole mouse embryos. Here, we combine an approach to make whole mouse embryos transparent, with multicolor marking, to allow observation of hematopoietic clusters using high-resolution 3-dimensional confocal microscopy. Our method provides the first complete map and temporal quantitation of all hematopoietic clusters in the mouse embryonic vasculature. We show that clusters peak in number at embryonic day 10.5, localize to specific vascular subregions and are heterogeneous, indicating a basal endothelial to non-basal (outer cluster) hematopoietic cell transition. Clusters enriched with the c-Kit-cell population contain functional hematopoietic progenitors and stem cells. Thus, three-dimensional cartography of transparent mouse embryos provides novel insight into the vascular subregions instrumental in hematopoietic progenitor/stem cell development, and represents an important technological advancement for comprehensive in situ hematopoietic cluster analysis.

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“…54 These common hematopoietic/endothelial (HE) precursors share an antigenic phenotype characterized by expression of the progenitor cell antigen, CD34, and VEGFR-2. 27,55 Murine gene knockout studies indicate that VEGFR-2 expression is required for vasculogenesis and for establishment of definitive hematopoiesis.…”

Section: Hemangioblast and Hematopoiesismentioning

confidence: 99%

Rational Approaches to Design of Therapeutics Targeting Molecular Markers

Klasa¹,

List²,

Cheson³

2001

Hematology

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This paper introduces novel therapeutic strategies focusing on a molecular marker relevant to a particular hematologic malignancy. Four different approaches targeting specific molecules in unique pathways will be presented. The common theme will be rational target selection in a strategy that has reached the early phase of human clinical trial in one malignancy, but with a much broader potential applicability to the technology.In Section I Dr. Richard Klasa presents preclinical data on the use of antisense oligonucleotides directed at the bcl-2 gene message to specifically downregulate Bcl-2 protein expression in nonHodgkin's lymphomas and render the cells more susceptible to the induction of apoptosis.In Section II Dr. Alan List reviews the targeting of vascular endothelial growth factor (VEGF) and its receptor in anti-angiogenesis strategies for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).In Section III Dr. Bruce Cheson describes recent progress in inhibiting cell cycle progression by selectively disrupting cyclin D1 with structurally unique compounds such as flavopiridol in mantle cell lymphoma as well as describing a new class of agents that affect proteasome degradation pathways.

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The embryonic origins of human haematopoiesis

Cited by 77 publications

References 79 publications

The origin and fate of yolk sac hematopoiesis: application of chimera analyses to developmental studies

The origin and fate of yolk sac hematopoiesis: application of chimera analyses to developmental studies

Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos

Rational Approaches to Design of Therapeutics Targeting Molecular Markers

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