Tracing the hemangioblast during embryogenesis: developmental relationships between endothelial and hematopoietic cells

Abstract

We review here the development of the hematopoietic system and its relationship to the endothelium, with a special focus on the characterisation of the hemangioblast, the putative ancestor for endothelial cells and hematopoietic cells. Using the avian model, we have traced in vivo the progeny of embryonic endothelial cells and shown that aortic-born hematopoietic cells (known to generate the definitive hematopoietic lineage) derive from endothelial cells in the floor of the aorta. During this process, endothelial cells undergo a switch from endothelial cells to hematopoietic cells characterised by a downgrading of endothelial cell-specific genes and the parallel upgrading of hematopoietic cell-specific genes. Using a similar approach, we have shown that generation of hematopoietic cells from endothelial cells also takes place during mouse embryonic development. We have thoroughly characterised the dynamics of key molecules (several of which we have cloned) specifically expressed by the yolk sac or aortic hemangioblast. The yolk sac hemangioblast is characterized by the specific expression of SCL/Tal-1 and Lmo2, whereas the aortic hemangioblast expresses Runx-1 (a runt domain transcription factor). Finally, we have demonstrated the existence of a new site for hematopoiesis, namely the allantois. Using quail/chick grafts, we show that this embryonic appendage autonomously produces endothelial cells and hematopoietic cells, these latter being endowed with the attributes of the definitive hematopoietic lineage.

Primitive and definitive erythropoiesis in the yolk sac: a birds eye view

“…Chick/quail and chick/chick chimera studies (Beaupain et al, 1979;Dieterlen-Lievre, 1975;Dieterlen-Lievre et al, 1976;Lassila et al, 1978;Lassila et al, 1982;Martin et al, 1978) and chick/chick parabiotic studies (Metcalf and Moore, 1971;Moore and Owen, 1965; indicated that, at least during the first few days of definitive erythrocyte generation, the source of cells is mainly yolk sac-derived. At about the same time, if not earlier, intraembryonic hematopoietic cells have been observed in association with the dorsal aorta (DieterlenLievre and Martin, 1981;Jaffredo et al, 2003;Jaffredo et al, 2005;Jaffredo et al, 2000;Jaffredo et al, 1998;Jordan, 1916;Nagai and Sheng, 2008;Olah et al, 1988;Pardanaud et al, 1996). A number of questions can be asked, for instance, about whether dorsal aorta-derived hematopoietic cells undergo definitive erythropoiesis either in circulation or in the yolk sac niche; whether yolk sac-derived hematopoietic cells can find their way to the dorsal aorta; and what is the exact type of cells from the yolk sac that contribute to early definitive erythropoiesis.…”

Commitment of hematopoietic stem cells in avian and mammalian embryos: an ongoing story

“…This provocative double colonization may mean either that distinct precursors of the two lineages travel through the circulation or that a common progenitor, the hemangioblast, is the cell that circulates and differentiates into the bone marrow microenvironment along the two pathways. Experimental arguments for the existence of the hemangioblast are accumulating (see Jaffredo et al, 2005 andEichmann et al, 2005, both in this issue), supporting the second interpretation. This finding in the avian model should be put together with the fact that endothelial progenitors bearing the HSC-specific antigen CD34 are known to circulate in the blood of the adult mouse during repair processes (Asahara et al, 1997;Raffii, 2000).…”

“…The rules thus uncovered were later extended to mammals. In the present volume, the articles by Jaffredo et al, 2005;Pudlewski andGodin andCumano, 2005 cover extensively the findings of my group about the commitment of HSC and their developmental relationship with the endothelial network in bird and mouse embryos. Here I shall put the history of these investigations in perspective, dwelling more lengthily on some issues not discussed in these articles and I will describe novel data about mouse embryo developmental hematopoiesis.…”

Stem Cells and the Temporal Boundaries of Development: Toward a Species-Dependent View

“…Second, the transition from pluripotency to multipotency is probably continuous. For example, the multipotent hematopoietic stem cell (i.e., tissue-specific stem cell of the hematopoietic system) comes from a ''hemangioblast'' which is in between the pluripotent stem cell of the ICM and the multipotent stem cell of the hematopoietic system (Jaffredo et al 2005;Xiong 2008). Pluripotency is a very elusive stage of stem cells but the difficulty can be partly avoided by determining the boundary between the second and the third stage through the beginning of the third stage, which can be identified with precision.…”