http://repub.eur.nl/res/aut/37712/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37497/ 2012-10-25T00:00:00Z The development of cell biology research coincides with the advance of microscopes in the 19th century. It was finally possible to directly observe the various blood cell types and to witness their proliferation and differentiation (Mazzarello, 1999). On the basis of his observations, the German pathologist Franz E.C. Neumann (1834–1918) suggested that the site of blood formation was the bone marrow (BM). He also proposed the pioneer theory in which one cell might be at the origin of all blood cell lineages. The Russian scientist Alexander A. Maximow (1874–1928) also developed and introduced the theory of a common cell for the complete blood-building system or hematopoiesis (Maximow, 1909). The concept of Hematopoietic Stem Cells (HSCs), although very controversial at the time, was born and has led to the beginning of stem cell research (Ramalho-Santos and Willenbring, 2007). http://repub.eur.nl/res/pub/30979/ 2012-01-01T00:00:00Z Hematopoietic Stem Cells (HSCs) are responsible for the production and replenishment of all blood cell types during the entire life of an organism. Generated during embryonic development, HSCs transit through different anatomical niches where they will expand before colonizing in the bone marrow, where they will reside during adult life. Although the existence of HSCs has been known for more than fifty years and despite extensive research performed in different animal models, there is still uncertainty with respect to the precise origins of HSCs. We review the current knowledge on embryonic hematopoiesis and highlight the remaining questions regarding the anatomical and cellular identities of HSC precursors. http://repub.eur.nl/res/pub/33440/ 2011-05-12T00:00:00Z CD41 expression is associated with the earliest stages of mouse hematopoiesis. It is notably expressed on some cells of the intra-aortic hematopoietic clusters, an area where the first adult-repopulating hematopoietic stem cells (HSCs) are generated. Although it is generally accepted that CD41 expression marks the onset of primitive/definitive hematopoiesis, there are few published data concerning its expression on HSCs. It is as yet uncertain whether HSCs express CD41 throughout development, and if so, to what level. We performed a complete in vivo transplantation analysis with yolk sac, aorta, placenta, and fetal liver cells, sorted based on CD41 expression level. Our data show that the earliest emerging HSCs in the aorta express CD41 in a time-dependent manner. In contrast, placenta and liver HSCs are CD41-. Thus, differential and temporal expression of CD41 by HSCs in the distinct hematopoietic territories suggests a developmental/dynamic regulation of this marker throughout development. http://repub.eur.nl/res/pub/27321/ 2010-02-16T00:00:00Z Haematopoietic stem cells (HSCs), responsible for blood production in the adult mouse, are first detected in the dorsal aorta starting at embryonic day 10.5 (E10.5). Immunohistological analysis of fixed embryo sections has revealed the presence of haematopoietic cell clusters attached to the aortic endothelium where HSCs might localize. The origin of HSCs has long been controversial and several candidates of the direct HSC precursors have been proposed (for review see ref. 7), including a specialized endothelial cell population with a haemogenic potential. Such cells have been described both in vitro in the embryonic stem cell (ESC) culture system and retrospectively in vivo by endothelial lineage tracing and conditional deletion experiments. Whether the transition from haemogenic endothelium to HSC actually occurs in the mouse embryonic aorta is still unclear and requires direct and real-time in vivo observation. To address this issue we used time-lapse confocal imaging and a new dissection procedure to visualize the deeply located aorta. Here we show the dynamic de novo emergence of phenotypically defined HSCs (Sca1+, c-kit+, CD41+) directly from ventral aortic haemogenic endothelial cells.