Generation of an inter-lineage cross-talk model of haematopoietic stem cell development
Project type
PhD
| Supervisor(s) | Division | |
| (Primary) | Molecular Medicine | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Molecular Medicine | .(JavaScript must be enabled to view this email address) |
Details of project
Mature blood cells have multiple functions ranging from transporting oxygen around the body to protecting us from infection. The ability to continue producing enough blood cells throughout life is critical to our health. This process is known as haematopoiesis (blood production). At the foundation of blood cell production is the haematopoietic stem cell (HSCs); these cell types are not specialised for any function except to ensure that when necessary large mature blood cells can be readily generated. An important question that remains unanswered is how HSCs are produced in the first place.
Haematopoietic progenitor and stem cell development in the embryo follows an exquisitely defined temporal and spatial pattern. This process of de novo haematopoiesis is initiated in an organ known as the yolk sac before in proceeds to the embryo proper. To understand how haematopoietic progenitor and stem cells are first produced we are interested in studying how they interact with their neighboring cells. To tackle this question we will generate bioinformatic predications of potential mechanisms of inter-lineage cross-talk; these predictions will then be tested using both in vivo and in vitro models of haematopoietic progenitor and stem cell development.
Research interests
Our laboratories are interested in studying the cellular and molecular mechanisms that drive haematopoietic stem cell (HSC) development during embryogenesis. If we can understand how the embryonic environment communicates with the ancestors of the HSC lineage to facilitate their formation we might be able to replicate this process in a culture dish. Such developments could be used to generate enough material for successful patient-specific HSC transplantation.
Selected publications
- Medvinsky A, Rybtsov S, and Taoudi S. Embryonic origin of the adult hematopoietic system: advances and questions. Development. 2011 138(6): 1017-1031.
- Taoudi S, Bee T, Hilton A, Knezevic K, Scott J, Willson TA, Collin C, Thomas T, Voss AK, Kile BT, et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 2011 25(3): 251-262.
- Taoudi S, Gonneau C, Moore K, Sheridan JM, Blackburn CC, Taylor E, and Medvinsky A. 2008. Extensive hematopoietic stem cell generation in the AGM region via maturation of VE-cadherin+CD45+ pre-definitive HSCs. Cell Stem Cell. 3(1): 99-108.
- Taoudi S and Medvinsky A. Functional identification of the hematopoietic stem cell niche in the ventral domain of the embryonic dorsal aorta. Proc Natl Acad Sci USA. 2007 104(22): 9399-9403.
- Taoudi S, Morrison AM, Inoue H, Gribi R, Ure J and Medvinsky A. 2005. Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver. Development. 132(18): 4179-4191.
Research theme
Cancer
Scientific discipline
- Developmental Biology
- Haematology
- Stem Cell Biology
Keywords
Haematopoiesis, stem cell development