Interrogating the importance of x-chromosome inactivation and reactivation for meiotic potential
X-chromosome dosage compensation in female mammals is achieved through X-chromosome inactivation (XCI), where one X chromosome is epigenetically silenced to ensure dosage parity with male cells. During germline development, this silenced X chromosome reactivates before the onset of meiosis, however...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/692844 |
| Acceso en línea: | http://hdl.handle.net/10803/692844 |
| Access Level: | acceso embargado |
| Palabra clave: | Stem cells Germline X chromosome Meiosis Methylation Células madre Línea germinal Cromosoma X Metilación 576 |
| Sumario: | X-chromosome dosage compensation in female mammals is achieved through X-chromosome inactivation (XCI), where one X chromosome is epigenetically silenced to ensure dosage parity with male cells. During germline development, this silenced X chromosome reactivates before the onset of meiosis, however the exact requirements for this remain to be fully characterised. In this thesis, I investigate the significance of X-chromosome dosage regulation in the female germline using an in vitro approach. We generated a dual X-chromosome reporter mouse embryonic stem cell line with a knockout of Xist, the long non-coding RNA responsible for mediating XCI. Our results demonstrate that most cells fail to maintain two active X chromosomes upon exiting pluripotency, leading to either X-chromosome loss or cell death. However, a subset of primordial germ cell-like cells (PGCLCs) that survive this bottleneck with two active X chromosomes progress efficiently to meiosis prophase I. Additionally, we find that X-chromosome dosage significantly influences the transcriptomic and epigenetic landscapes of PGCLCs. These findings offer new insights into the epigenetic prerequisites for proper meiotic entry in female germ cells and underscore the critical role of X-chromosome dosage in germline development. |
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