Mechanistic Roles of PUF-8 and Its Partners in Controlling Germline Stem Cell Maintenance and Differentiation in Caenorhabditis elegans
| Author/creator | Norman, Mina author |
| Other author | Lee, Myon Hee degree supervisor. |
| Other author | East Carolina University |
| Format | Theses and dissertations |
| Publication | [Greenville, N.C.] : [East Carolina University 2026.] |
| Description | 104 pages |
| Supplemental Content | Access via ScholarShip |
| Summary | Stem cells are highly regulated by conserved extrinsic and intrinsic regulators. Among these regulators, cell cycle regulators and PUF proteins play a crucial role in cell fate and the maintenance of stem cells; however, their functional interplay remains poorly understood. Of the 11 PUF proteins in C. elegans, PUF-8 is most closely related to human PUF proteins PUM1 and PUM2. Within the germline, PUF-8 collaborates with additional regulators to control germline stem cell (GSC) proliferation, differentiation, and maintenance. This research demonstrates that both CYB-3/CDK-1 and CYE-1/CDK-2, as well as PUF-8, are required for GSC maintenance during both early germline development and adult germline. RNAi-mediated knockdown of cyb-3, cdk-1, cye-1, or cdk-2 in puf-8 mutants results in proliferation and maintenance defects of GSCs. Additionally, PUF-8 and these cell cycle regulators protect meiotic cells from CED-4-mediated apoptosis. Furthermore, we elucidate the roles of PUF-8, CYB-3/CDK-1, and CYE-1/CDK-2 across three germline tumor models driven by ectopic proliferation, failure of meiotic entry, or dedifferentiation. In all three contexts, PUF-8 and these associated cell cycle regulators suppress germline tumor formation and maintenance. We further investigated dedifferentiation-mediated tumorigenesis and its regulation by the chemical tert-Butylhydroquinone (tBHQ) and R-loop repressors, RNH-1/2 and BRC-1/2. In puf-8 mutant germlines, dedifferentiation-mediated tumorigenesis depends on MPK-1 signaling. Interestingly, under high-glucose conditions, tBHQ increases the level of phosphorylated MPK-1b, thereby enhancing dedifferentiation-mediated tumorigenesis. The mechanisms by which glucose and tBHQ synergize to promote tumor formation remain unknown. We further show that R-loop repressors and PUF-8 are required to suppress aberrant R-loop accumulation, thereby preventing dedifferentiation-mediated tumorigenesis. Together, these results provide deeper insight into the interplay between dedifferentiation and tumorigenesis. |
| Dissertation note | East Carolina University 2026. |
| Bibliography note | Includes bibliographical references. |
| Technical details | System requirements: Adobe Reader. |
| Technical details | Mode of access: World Wide Web. |
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| Library | Location | Call Number | Status | Item Actions |
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| Electronic Resources | Access Content Online | ✔ Available |