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Title: Studying the role of B-Myb during somatic reprogramming and in iPSCS
Author: Ward, Carl Ross James
ISNI:       0000 0004 5367 3743
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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Somatic cell reprogramming towards a pluripotent stem cell-like state occurs in an organized way, with rapid changes in gene expression during the first days of induction. Little is known about the mechanisms that lead to DNA double strand breaks (DSB) and genome instability during reprogramming. Amongst genes upregulated during reprogramming is that encoding the transcription factor B-Myb. \(B\)-\(myb\) RNA levels increase gradually from day 2 of reprogramming, earlier than those encoding pluripotency factors such as \(Nanog\). Despite its possible function as a regulator of the pluripotent state, B-Myb has a general role in the regulation of proliferation, and genome stability throughout the animal kingdom, raising the possibility that the activity of this protein is linked to the DSBs observed during reprogramming. To explore this possibility, reprogramming studies were performed in which B-Myb expression was modified: B-\(myb\)-/- MEFs were incapable of reprogramming after transduction with OSKM lentivirus (Oct4/Sox2/Klf4/c-Myc). However, unexpectedly, co-expression of B-Myb together with OSK (OSKB lentivirus), severely impaired the efficiency of reprogramming. Interestingly, the iPSC colonies appeared more ESC-like and had less DSBs. My results show that both the level of the B-Myb expression is crucial during early stages of reprogramming, indicating that B-Myb is a gatekeeper for reprogramming.
Supervisor: Not available Sponsor: Medical Research Council ; Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics ; QR180 Immunology ; R Medicine (General)