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dc.contributor.advisorTurner, Marc
dc.contributor.advisorMedvinsky, Alexander
dc.contributor.authorIvanovs, Andrejs
dc.date.accessioned2014-05-23T13:20:35Z
dc.date.available2014-05-23T13:20:35Z
dc.date.issued2012-11-30
dc.identifier.urihttp://hdl.handle.net/1842/8839
dc.description.abstractHaematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Qualitative and quantitative assessment of HSCs can only be performed functionally using the in vivo long-term repopulation assay. Due to the lack of such data, little is known about the development of HSCs in the human embryo, which is a prerequisite for the development of new therapeutic strategies. Employing the xenotransplantation assay, I have performed here the spatio-temporal mapping of HSC activity within the human embryo and have shown that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the ventral wall of the dorsal aorta, and only later appear in the yolk sac, liver and placenta. Human AGM region HSCs transplanted into immunodeficient mice provide long-term high-level multilineage haematopoietic repopulation. These cells, although present in the AGM region in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates around 600 daughter HSCs in primary recipient mice, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine. I have also established a preliminary immunophenotype of the earliest human HSC. These data will be useful for my future studies on the mechanisms underlying the high potency of human embryonic HSCs and on the characterisation of embryonic HSC niche.en_US
dc.contributor.sponsorMedical Research Council (MRC)en_US
dc.contributor.sponsorLeukaemia and Lymphoma Researchen_US
dc.contributor.sponsorBiotechnology and Biological Sciences Research Council (BBSRC)en_US
dc.contributor.sponsorWellcome Trusten_US
dc.language.isoenen_US
dc.publisherThe University of Edinburghen_US
dc.relation.hasversionRybtsov, S., Sobiesiak, M., Taoudi, S., Souilhol, C., Senserrich, J., Liakhovitskaia, A., Ivanovs, A., Frampton, J., Zhao, S., and Medvinsky, A. (2011). Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region. J Exp Med 208, 1305-1315.en_US
dc.subjecthuman embryo AGM regionen_US
dc.subjectHaematopoietic stem cellsen_US
dc.subjectHSCsen_US
dc.subjectstem cellsen_US
dc.subjectHaematopoiesisen_US
dc.titleDevelopment of haematopoietic stem cells in the human embryoen_US
dc.typeThesis or Dissertationen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US


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