To characterise the role of RTEL1 DNA helicase in the maintenance of intestinal stem/progenitor cells

dc.contributor.authorSeshadri, Nivedita
dc.contributor.examiningcommitteeOgilvie, Tamara (Biochemistry and Medical Genetics) Klonisch, Thomas ( Human Anatomy and Cell Science)en_US
dc.contributor.supervisorDing, Hao (Biochemistry and Medical Genetics)en_US
dc.date.accessioned2015-02-05T22:11:51Z
dc.date.available2015-02-05T22:11:51Z
dc.date.issued2015-02-05
dc.degree.disciplineBiochemistry and Medical Geneticsen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractRTEL1 (Regulator of telomere length1) DNA helicase has been demonstrated to be vital for the maintenance of telomere length and genomic stability. However, its biological role during development is unknown. Our recent finding that RTEL1 is selectively expressed in several types of adult stem cells, suggests that RTEL1 could play an essential role in the maintenance of these cells. Depending on the function of RTEL1 in the maintenance of genomic stability, we hypothesize that RTEL1 could be required for protecting adult stem cells from genomic instability, whose dysfunction may not only impair tissue homeostasis/regeneration, but also could transform these cells to form tumors. In this study, we have used mouse intestinal stem/progenitor cells model to address this hypothesis. With a transgenic lineage tracing assay, we demonstrated that RTEL1-expressing cells in intestinal crypts can self renew and differentiate to the progeny cells required for intestinal homeostasis. Using a conditional knockout approach, we also showed that loss of RTEL1 function could induce genomic instability in intestinal stem/progenitor cells, which significantly affected the survival of intestinal stem cells and intestinal regeneration. Finally, in this study, we also observed intestinal hyperplasia in our RTEL1 conditional knockout mice, indicating that loss of RTEL1 function may initiate intestinal tumorigenesis. All of these findings strongly support that RTEL1 could be one the key molecules necessary for the maintenance of intestinal stem/progenitor cells and this function could be important for preventing intestinal tumorigenesis.en_US
dc.description.noteMay 2015en_US
dc.identifier.urihttp://hdl.handle.net/1993/30263
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectintestinal stem cellsen_US
dc.subjectRTEL1en_US
dc.titleTo characterise the role of RTEL1 DNA helicase in the maintenance of intestinal stem/progenitor cellsen_US
dc.typemaster thesisen_US
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