Saudi Cultural Missions Theses & Dissertations
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Item Restricted Novel Strategy to Unlock Transgenerational Stress Memory in Clonal Plants(warwick university, 2024) Alotaibi, Hidayah; Gutierrez-Marcos, JoséBeing sessile organisms, plants are exposed to a wide range of environmental stress conditions. Recent studies have shown that plants can store information about environmental stresses and access this associated memory to mount a primed response that offers protection from subsequent stress events. This ‘stress memory’ is thought to be mediated by epigenetic modifications, which in turn modulate gene expression, phenotype, and metabolism. However, these environmentally directed epigenetic changes although they are integrated into somatic cells, they are short-lived and/or actively reset during sexual reproduction. Notably, using Arabidopsis as a model system we have recently found that clonal plants generated using zygotic transcription factors display epigenetic and transcriptional features present in the founder cells used for regeneration. Moreover, these molecular signatures are stably transmitted over multiple generations of sexual reproduction, creating distinct phenotypic variants. Therefore, we hypothesised that cloning from somatic cells exposed to distinct environmental stimuli could be used to engineer specific primed responses in plants. To test this hypothesis, we have generated clonal lines from tissues exposed to a short abiotic stress pulses that were propagated sexually over three generations in stress free conditions. Our data shows clonal plants derived from primed tissues display a transgenerational stress memory response, which is associated with specific transcriptional states, and enhanced tolerance under stress. Our study also aiming to identify the molecular mechanisms implicated in the integration, storage and retrieval of the acquired stress memory with the aim of engineering specific primed responses in plants. Our data shows that the transcriptional activity of DREB2A genes is necessary and partly sufficient for a salt-induced transgenerational salt memory in clonal plants46 0Item Restricted What Does MicroRNA Expression Say about Human Preimplantation Blastocysts: A Descriptive Analytical Study(University College London, 2024) Almutlaq, Arwa; SenGupta, SiobanEmbryo quality is critical in in vitro fertilization treatment, significantly influencing the pregnancy success. While preimplantation genetic testing offers a reliable assessment of embryonic chromosomal status, the investigations of the embryo’s molecular characteristics remain less implemented. MiRNAs, known for their post- transcription regulatory functions, have emerged as promising markers for genetic disruptions. These small non-coding RNAs found both inside and outside cells and typically exhibit altered profiles in disorders with genetic abnormalities. In this study, we utilised next-generation sequencing to explore the miRNA expression profile in 122 cryopreserved human blastocysts collected from CRGH, London. The comprehensive miRNA profiling revealed abundant and stable miRNAs expression in blastocysts, with a substantial increase in the levels of miRNAs encoded in key miRNA clusters, such as C19CM and miR-17/92. Functional analysis linked these miRNAs to crucial biological pathways, including protein modification, cell cycle progression, response to low oxygen levels, and apoptosis. A series of differential miRNAs expression analyses were conducted to identify potential associations between miRNA expression and embryo competence. The findings revealed consistent and significant dysregulation in the miRNA profile in blastocysts with various types of aneuploidies compared to euploid ones. Additionally, differences in miRNA levels were observed among blastocysts at different blastulation days (day5 versus day 6) and between those with varying TE morphology grades. The miRNA expression profile was also assessed in relation to parental factors known to influence implantation potential and pregnancy outcomes. The results indicated that advanced reproductive age, both maternal and paternal, high ovarian stimulation dosage and impaired sperm parameters are potentially associated with altered miRNA expression in the examined blastocysts. Notably, one miRNA, hsa- miR-184, was consistently upregulated across these investigations. The dysregulated miRNAs in these analyses were commonly involved in cell cycle dynamics, metabolic processes and signalling pathways. Understanding the molecular differences between good- and poor-quality embryos through miRNA expression could enhance our knowledge of the underlying causes of poor embryonic development and outcomes. Hypothetically, these miRNAs hold promise as biomarkers for evaluating the quality of preimplantation blastocysts, contributing to advancements in reproductive treatment.8 0Item Restricted Analysing the contribution of Wt1-expressing cells in the development of the vascular and visceral smooth muscle in mouse embryos and gastruloids(2023) Alghamdi, Suad Hassan S; Wilm, Bettina; Turner, David; Cross, Michael; Butts, ThomasDuring embryonic development, the epicardium, the mesothelium of the heart, contributes vascular smooth muscle cells (VSMCs) to the coronary vessels; however, the developmental origin of VSMCs in the embryo is not clearly defined. A previous study had reported that cells expressing the Wilms’ tumour protein (Wt1), a key marker of mesothelia, give rise to VSMCs in the intestine, mesentery, and coronary vessels, using genetic lineage tracing experiments (Wilm et al., 2005). Because Wt1 is expressed in the mesothelium of the body cavities, we concluded that Wt1-expressing mesothelial cells contributed to the VSMC compartment in the respective organs. Further studies analysing Wt1 lineage contribution led to the finding that Wt1 is switched on and remains expressed in the visceral mesothelium from around E9.5 onwards, while earlier transient expression of Wt1 in the nascent mesoderm specifies the future vascular and visceral smooth muscle of the intestine and mesentery (Wilm et al., 2021, Alghamdi et al., 2020). These results have revealed that the VSMC lineage is more complicated. In order to determine the contribution of Wt1-expressing cells to the VSMC lineage, this study used temporally controlled lineage-tracing experiments based on a Tamoxifen-inducible reporter system for different embryonic stages between 18.5 and 8.5 of embryonic development. Our lineage tracing of Wt1-expressing cells tagged at E8.5 and followed to different stages of embryonic development revealed their VSMC fate, with only a few visceral mesothelial cells found to be GFP-positive. Data of this thesis suggests that Wt1 expression before or during the initial phase of mesothelium formation in the intermediate and lateral plate mesoderm marks the cells that will become VSMCs. Furthermore, analysis of Wt1GFP/+ embryos at E8.5 was found to have some cells in the mesoderm and the primitive streak. This suggests a more intricate role for Wt1 in the lineage tracing of VSMCs that expressed Wt1. Further analysis of the Wt1-expressing mesoderm population was performed by using gastruloids generated from mouse embryonic stem cells (ESCs) as a valuable in vitro tool to study early embryonic development. We labelled gastruloid with different intermediate, lateral plate, and paraxial mesodermal markers to identify possible co-expression in the cells that expressed Wt1. Interestingly, gastruloids cultured for 72h and 96h showed co-expression of Wt1 and the mesodermal markers in the same region, while after 96h of culture, some of these cells appeared to have migrated to the anterior part of the gastruloid while other cells remained in the posterior part identified by expression of the early mesoderm marker Brachyury. This separation seemed to be completed in 120h gastruloids, which are thought to be equivalent to embryos at between E7.5 and E8.5, as the Wt1 expression only presented in the anterior side of the gastruloid. These findings led us to conclude that the origin of the Wt1-expressing cells that give rise to VSMSC in the intestine and the mesentery appears to be a posterior mesodermal-derived progenitor cell population. These progenitor cells then follow a specific journey during the next stages of embryonic development.32 0