Development of haematopoietic stem cells in the human embryo
dc.contributor.advisor
Turner, Marc
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dc.contributor.advisor
Medvinsky, Alexander
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dc.contributor.author
Ivanovs, Andrejs
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dc.contributor.sponsor
Medical Research Council (MRC)
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dc.contributor.sponsor
Leukaemia and Lymphoma Research
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dc.contributor.sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
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dc.contributor.sponsor
Wellcome Trust
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dc.date.accessioned
2014-05-23T13:20:35Z
dc.date.available
2014-05-23T13:20:35Z
dc.date.issued
2012-11-30
dc.description.abstract
Haematopoietic 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
dc.identifier.uri
http://hdl.handle.net/1842/8839
dc.language.iso
en
dc.publisher
The University of Edinburgh
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dc.relation.hasversion
Rybtsov, 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.
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dc.subject
human embryo AGM region
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dc.subject
Haematopoietic stem cells
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dc.subject
HSCs
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dc.subject
stem cells
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dc.subject
Haematopoiesis
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dc.title
Development of haematopoietic stem cells in the human embryo
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dc.type
Thesis or Dissertation
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dc.type.qualificationlevel
Doctoral
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dc.type.qualificationname
PhD Doctor of Philosophy
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