The regulation of human β-globin gene switching by promoter competition

Jeantet, Valentine (2019) The regulation of human β-globin gene switching by promoter competition. PhD thesis, University of Glasgow.

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Blood transfusions are a major lifesaving aspect of modern medicine and rely on voluntary blood donations. However, a worldwide shortage of blood donations along with the risk of transmission of infectious diseases led scientists to research how to generate blood in the laboratory using stem cells or progenitor cells. Amongst the limitations they are faced with is the fact that human embryonic stem cells, due to their origin, produce reticulocytes expressing foetal rather than adult haemoglobin, caused by developmentally regulated genes at the β-globin locus.
This cluster consists of five β-like globin genes arranged sequentially in the order they are expressed during development. Reticulocytes derived from cord blood haematopoietic stem cells or embryonic pluripotent stem cells primarily express the foetal γ- and embryonic ε-globin genes. Many non-exclusive models have been described such as gene competition, locus control region (LCR) looping and transcription factors repression. Numerous studies have been carried out in humanised mice models and have shown that genetic manipulations of the locus could activate adult β-globin expression.
Here, we used the CRISPR/Cas9 system to create different deletions or mutations at the β-globin locus in K562 cells, a human erythroid cancer cell line which expresses embryonic and foetal globin genes.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: West, Dr. Adam and Mountford, Dr. Joanne
Date of Award: 2019
Embargo Date: 18 April 2022
Depositing User: Ms Valentine Jeantet
Unique ID: glathesis:2019-41170
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 07:53
Last Modified: 30 Dec 2019 10:32
Thesis DOI: 10.5525/gla.thesis.41170

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