Blood stem cells arise from the aorta in chicken embryos

The Robin group published a paper in which they studied hematopoietic stem cells (HSCs), the stem cells at the origin of blood. They studied these cells during the development of chicken embryos and evaluated their contribution to the different types of blood cells in the adult chicken. The Robin group has shown that chicken HSCs arising out of the aorta (the largest artery in the body) during embryonic development are true HSCs that contribute to multiple types of blood cells. This shows that the development of HSCs is very similar between chicken and mammals and provides new opportunities to study blood stem cells.

HSCs, responsible for blood cell production throughout life, are initially generated during the embryonic development of vertebrates. Human and chicken embryos share features that position the chicken as a reliable and accessible alternative model to study developmental hematopoiesis. However, hematopoietic production is poorly described and the existence of HSCs has never been formally proven in chicken embryos. In this study, we first established a complete cartography and quantification of hematopoietic cells in the chicken embryonic aorta during development. By performing whole-mount fluorescent immunostaining and 3D reconstruction of whole aortas and chicken embryos, Laurent Yvernogeau and Catherine Robin show that hematopoietic cell emergence is a regulated process, both in time and space. It starts at embryonic day (E)2.25 along the anterior to posterior axis of the embryo and remains restricted to the ventral floor of the anterior portion of the aorta as development unfolds. Second, they developed a new in vivo transplantation assay named chorio-allantoic membrane (CAM) transplantation to identify and locate HSCs in the chicken embryo. This technique consisted of dissecting tissues from GFP donor embryos (aorta, yolk sac, allantois or head) and transplanting them into the CAM of wild type recipient embryos. The donor tissue, in contact to the CAM, connects to the recipient vasculature, allowing proper oxygenation and autonomous growth of the tissue. The use of GFP transgenic chicken allowed an easy tracking of donor cells within the grafted tissue and in the growing embryo recipient (after cell migration). The transplanted recipients hatched and grew until up to 5 months old when potent multilineage repopulation by GFP donor cells was tested. Yvernogeau and Robin demonstrated that similarly to mammals, true multilineage HSCs exist in the chicken embryo and that these cells originated from the aorta and not from the yolk sac, allantois or head.

Historically, most breakthrough discoveries in the field of developmental hematopoiesis were first made in birds and later extended to mammals. Combining the knowledge on chicken hematopoiesis, the HSC transplantation assay and gain/loss-of-function experiments should provide new insights into the regulation of HSCs in vivo. Accordingly, the avian model represents an exciting and powerful model to open new paths for future exciting breakthrough discoveries.

Dr. Catherine Robin is group leader at the Hubrecht Institute and is also associated with the UMC Utrecht.

Restricted intra-embryonic origin of bona fide hematopoietic stem cells in the chicken (PDF)
Authors: Laurent Yvernogeau and Catherine Robin
Development 2017 144: 2352-2363