Study of the role of cell-matrix force transmission in naive to primed pluripotency transition in mouse embryonic stem cells
[eng] “Doing the right thing, at the right time, to the right extent, in the right manner, and for the right purpose”. This isn’t a shoddy attempt at virtue signalling by invoking Aristotle. It rather is my philosophical understanding of embryonic development. During my formative years, being taught...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/214022 |
| Acceso en línea: | https://hdl.handle.net/2445/214022 http://hdl.handle.net/10803/691535 |
| Access Level: | acceso abierto |
| Palabra clave: | Bioenginyeria Cèl·lules mare embrionàries Interacció cel·lular Bioengineering Embryonic stem cells Cell interaction |
| Sumario: | [eng] “Doing the right thing, at the right time, to the right extent, in the right manner, and for the right purpose”. This isn’t a shoddy attempt at virtue signalling by invoking Aristotle. It rather is my philosophical understanding of embryonic development. During my formative years, being taught by biological purists led to me adopting a reductionist approach of looking for a biochemical effector and understanding its transduction through signalling pathways. While it has informed me greatly on the fine details of the biochemistry behind embryo morphogenesis, I was still left with lingering questions. How does a symmetrical and spherical embryo give rise to an organism whose development and survival needs asymmetry, be it in organ placement or overall bodily function? Is the genetic information flow the only mode of materializing the changes needed for embryonic development? Are there alternative sources of signalling cues other than soluble factors? Driven by this curiosity, I performed literature review during my masters and got introduced to the world of mechanobiology. I was intrigued by how physical forces regulate the timing, placement and extent of genetic information flow and confer robustness to embryonic development making it virtuous!! Importantly, it changed my perception of extracellular matrix (ECM) which until then I considered to play a passive role as a mere structural support. ECM deposition constituting a mechanical cue and the force transmission to ECM driving tissue morphogenesis evoked an interest to elucidate its functional role in early stages of embryonic development. As the foundation for all organs and tissues are laid by pluripotent epiblast, I wanted to understand how interaction with ECM regulates pluripotency dissolution and prepares for further stages of embryonic development. To achieve this, I joined Dr.Pere Roca-Cusachs’ lab and under the co-supervision of Dr. Zanetta Kechagia, I performed the current thesis work which is to study the role of cell-ECM force transmission in pluripotency transition in mouse embryonic stem cells. The thesis is divided into seven chapters. In the first chapter, an introduction to pluripotency and its dissolution, and the status quo on our understanding of pluripotency dissolution is mentioned. Having identified the key knowledge gaps, in the second chapter, the main objective of the study and the specific aims through which it is achieved are listed out. The third chapter deals with the experimental techniques and materials employed in the work. In the fourth, the results are listed out which suggest why force transmission to ECM is required for pluripotency dissolution. The detailed discussion of each experimental intervention and what they mean in light of the current knowledge along with potential future research directions to pursue are given in chapter five. In the sixth chapter, the key conclusions of the study are listed followed by chapter seven which is the bibliography. The results of this thesis are included in a manuscript for which I am a first author, and the manuscript is about to be submitted. To borrow the message of Martin A Schwart’s essay “The importance of stupidity in scientific research”, scientific pursuit is the process of being productive while confronting our ignorance. The end result is to garner wisdom and to acknowledge one’s absolute stupidity about research problems of higher difficulty. While performing this thesis work, I have always abided by this motto. With that being said, I wish you therefore enjoy reading the work by a “stupid of the highest order”. |
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