Endothelio-Mesenchymal Interaction Controls runx1 Expression and Modulates the notch Pathway to Initiate Aortic Hematopoiesis

Richard, Charlotte; Drevon, C.; Canto, Pierre-Yves; Villain, Gaëlle; Bollérot, Karine; Lempereur, Aveline; Teillet, Marie-Aimée; Vincent, Coralie; Rosselló, Catalina Ana; Torres, Miguel; Piwarzyk, Eileen; Speck, Nancy A.; Souyri, Michèle; Jaffredo, Thierry

doi:10.1016/j.devcel.2013.02.011

Cited by 95 publications

(98 citation statements)

References 61 publications

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“…However, RUNX1 is expressed in culture from D2, and its expression increases and extends to most, if not all, ECs thereafter. This is in keeping with the changes in RUNX1 expression shown to occur in vivo during the formation of the aorta (Richard et al, 2013), thereby demonstrating that our culture conditions accurately reproduce the cellular and molecular events taking place in vivo. When they undergo EHT, each culture produces de novo at least 2×10 4 cells per 35-mm dish per day from D4 to D8, and this number increases further to reach 1×10 5 cells per dish at D12, corresponding to a considerable hematopoietic production considering the relatively low number of cells seeded at culture onset.…”

Section: Discussionsupporting

confidence: 77%

“…Tracing experiments in vivo, including live imaging approaches, revealed a developmental relationship between ECs and hematopoietic clusters (Jaffredo et al, 1998;de Bruijn et al, 2002;Zovein et al, 2008;Chen et al, 2009;Bertrand et al, 2010;Boisset et al, 2010;Kissa and Herbomel, 2010;Lam et al, 2010). Cluster emergence relies on the presence of specialized ECs, termed hemogenic endothelial cells, which, upon appropriate signaling (Richard et al, 2013), lose their endothelial phenotype and acquire hematopoietic traits. This complex, multi-step developmental process was designated the endothelial-to-hematopoietic transition (EHT) (Kissa and Herbomel, 2010).…”

Section: Introductionmentioning

confidence: 99%

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An in vitro model of hemogenic endothelium commitment and hematopoietic production

et al. 2016

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Adult-type hematopoietic stem and progenitor cells are formed during ontogeny from a specialized subset of endothelium, termed the hemogenic endothelium, via an endothelial-to-hematopoietic transition (EHT) that occurs in the embryonic aorta and the associated arteries. Despite efforts to generate models, little is known about the mechanisms that drive endothelial cells to the hemogenic fate and about the subsequent molecular control of the EHT. Here, we have designed a stromal line-free controlled culture system utilizing the embryonic pre-somitic mesoderm to obtain large numbers of endothelial cells that subsequently commit into hemogenic endothelium before undergoing EHT. Monitoring the culture for up to 12 days using key molecular markers reveals stepwise commitment into the blood-forming system that is reminiscent of the cellular and molecular changes occurring during hematopoietic development at the level of the aorta. Long-term single-cell imaging allows tracking of the EHT of newly formed blood cells from the layer of hemogenic endothelial cells. By modifying the culture conditions, it is also possible to modulate the endothelial cell commitment or the EHT or to produce smooth muscle cells at the expense of endothelial cells, demonstrating the versatility of the cell culture system. This method will improve our understanding of the precise cellular changes associated with hemogenic endothelium commitment and EHT and, by unfolding these earliest steps of the hematopoietic program, will pave the way for future ex vivo production of blood cells.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

An in vitro model of hemogenic endothelium commitment and hematopoietic production

et al. 2016

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“…Expression of Gli1, one of the intracellular effectors of hedgehog signaling, is most prominent in subaortic mesenchymal cells, suggesting that the positive effect of hedgehog signaling derived from the gut acts via mesenchymal cells. Indeed, the role of the subaortic mesenchyme in inducing Runx1 expression and intra-aortic cluster formation was recently demonstrated in grafting experiments in the avian system [105].…”

Section: Signals From Cells In the Gutmentioning

confidence: 96%

Concise Review: From Greenhouse to Garden: The Changing Soil of the Hematopoietic Stem Cell Microenvironment During Development

2014

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The hematopoietic system has been intensely studied for many decades. For this reason, it has become the best understood stem cell-derived system that serves as a paradigm for stem cell biology and has found numerous applications in the clinics. While a lot of progress has recently been made in describing the bone marrow components that maintain and control blood stem cell function in the adult, very little is currently known about the regulatory microenvironment in which the first adult-repopulating hematopoietic stem cells are formed during development. Knowledge of these processes is crucial for understanding the basic regulation of hematopoietic stem cell production and behavior and to allow their in vitro expansion and generation from embryonic stem cells or iPS cells for clinical and research purposes. This review summarizes the recent advances that have been made in defining the cellular components, as well as the soluble and physical factors, that are part of the niche involved in regulating hematopoietic stem cell generation in the embryo. The findings are compared with what is known about the adult bone marrow niche to find common pathways for stem cell regulation, but also to highlight processes uniquely required for de novo hematopoietic stem cell generation, as these are the conditions that will need to be recreated for the successful production of blood stem cells in culture.

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“…The chick embryo has long been instrumental in this type of study. Recently, the Jaffredo group employed intricate dissections and labelling studies to reveal a requirement for the ventral sub-aortic mesoderm for the induction of Runx1 expression and the formation of intra-aortic clusters, independent of aortic specification [73].…”

Section: The Microenvironment Supporting Ehtmentioning

confidence: 99%

A short history of hemogenic endothelium

Swiers

Rode

Azzoni

et al. 2013

Blood Cells, Molecules, and Diseases

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Definitive hematopoietic cells are generated de novo during ontogeny from a specialized subset of endothelium, the so-called hemogenic endothelium. In this review we give a brief overview of the identification of hemogenic endothelium, explore its links with the HSC lineage, and summarize recent insights into the nature of hemogenic endothelium and the microenvironmental and intrinsic regulators contributing to its transition into blood. Ultimately, a better understanding of the processes controlling the transition of endothelium into blood will advance the generation and expansion of hematopoietic stem cells for therapeutic purposes.

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Endothelio-Mesenchymal Interaction Controls runx1 Expression and Modulates the notch Pathway to Initiate Aortic Hematopoiesis

Cited by 95 publications

References 61 publications

An in vitro model of hemogenic endothelium commitment and hematopoietic production

An in vitro model of hemogenic endothelium commitment and hematopoietic production

Concise Review: From Greenhouse to Garden: The Changing Soil of the Hematopoietic Stem Cell Microenvironment During Development

A short history of hemogenic endothelium

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