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dc.contributor.authorZaidan, Nada Mousa O
dc.date.accessioned2018-04-03T13:51:02Z
dc.date.available2018-04-03T13:51:02Z
dc.date.issued2018-07-31
dc.date.submitted2017-09-29
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274544
dc.description.abstractThe first definitive haematopoietic stem cells (HSCs) produced during embryonic development are generated from a specialised subset of endothelial cells known as haemogenic endothelium. Recently, it was reported that Gata3 plays a dual role in the development of sympathetic nervous system and haematopoietic system. In fact, Gata3 has proven to be crucial for the production of HSCs through regulation of catecholamine production from the co-developing sympathetic nervous system. Also, it was recently shown that Gata3 is expressed in the haemogenic endothelium and haematopoietic progenitor cells. Here, I will specifically examine the role of Gata3 in the production of HSCs; if it is expressed and plays a role in the precursors from which HSCs arise. Using a Gata3-GFP reporter mouse line, we found that Gata3 is expressed in various cell types in the HSCs microenvironment, including mesenchymal cells, endothelial cells, haematopoietic cells and sympathetic nervous system, and this expression was stage dependant. In the endothelial cells, we have found that the haemogenic endothelium activity is enriched in Gata3 expressing cells. Within the haematopoietic cells, we have found that Gata3 marks a specific stage along the developmental pathway towards the generation of definitive haematopoietic stem cells, and that Gata3 expressing haematopoietic cells are enriched for the most immature and stem cell like progenitors. Moreover, Gata3 will be specifically knocked out in haemogenic endothelial cells to determine whether it plays an essential role in the production of HSCs from the endothelium using the Vec-Cre system. We found that Gata3 within the haemogenic endothelium plays a major role in haematopoietic progenitors formation, and possibly haematopoietic stem cell formation. Finally, we used molecular assay (RNA seq) to identify the role of Gata3 in the haematopoietic stem cell microenvironment and found that Gata3 plays a major role in the development and differentiation of various cells and systems, and implicated Gata3 as cell cycle regulator. In summary, we found that Gata3 expressing cells is enriched for haemogenic endothelium, crucial for the haematopoietic progenitors formation, plays and important role in endothelial to haematopoietic transition, and plays a key developmental role in both haematopoietic stem cell and its microenvironment.
dc.description.sponsorshipKing Abdullah International Medical Research Centre Ministry of National Guards - Health Affairs, Riyadh, Saudi Arabia
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectAGM
dc.subjectCD34
dc.subjectCD41
dc.subjectCD43
dc.subjectCD45
dc.subjectCFU-C
dc.subjectCFU-M
dc.subjectCFU-Mix
dc.subjectCFU-GM
dc.subjectE
dc.subjectEE
dc.subjectEHT
dc.subjectDO
dc.subjectdHSC
dc.subjectFACS
dc.subjectFL
dc.subjectGata3
dc.subjectGFP
dc.subjectHE
dc.subjectHSPC
dc.subjectHSC
dc.subjectP75
dc.subjectPAS
dc.subjectPDGRb
dc.subjectTh
dc.subjectVE-Cad
dc.subjectYS
dc.subjectMSC
dc.titleThe Role of Gata3 in Blood Stem Cell Emergence
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentDepartment of Haematology
dc.date.updated2018-04-02T01:13:29Z
dc.identifier.doi10.17863/CAM.21678
dc.publisher.collegeMurray Edwards
dc.type.qualificationtitlePhD
cam.supervisorGottgens, Berthold
cam.thesis.fundingfalse
rioxxterms.freetoread.startdate2019-04-03


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