Effect of Sirt1 and telomerase on stem cells
| Autor: | Coussens, Matthew J |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | Diplomová práce |
| Popis: | Thesis (Ph.D.)--University of Hawaii at Manoa, 2008. Two genes that have established roles in the regulation of cell survival are telomerase reverse transcriptase (Tert) and the nicotinamide adenine dinucleotide-dependent protein deactylase Sirt1. However, the relative importance of these genes to the survival of stem cells, and the regulation of expression of these genes in stem cells, has yet to be thoroughly established. We now show that telomerase suppression in quiescent male primordial germ cells (PGCs) from murine embryos is accompanied by a decrease in expression of TERT. Telomerase activity was detected in quiescent PGCs from transgenic embryos, that constitutively express TERT, demonstrating that re-activation of TERT expression is sufficient to restore telomerase activity in these cells and implying that TERT expression is an important mechanism of telomerase regulation in PGCs. These results also demonstrate that TERT per se does not affect proliferation or development of PGCs in mammals, Sirt1, a member of the sirtuin family of proteins, orthologous to the yeast Sir2, has important physiological roles in regulating glucose metabolism. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/-) mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Microarray analysis in Sirt1 deficient testis revealed dysregulated expression of 85 genes, which were enriched (P Includes bibliographical references (leaves 117-132). Also available by subscription via World Wide Web 132 leaves, bound 29 cm |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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