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Mechanisms of niche to stem cell conversion exemplified by the follicle stem cell lineage in Drosophila melanogaster
Proper tissue homeostasis is often regulated and maintained by stem cells, which undergo self-renewal to furthermore produce differentiating daughter cells. Tissues are exposed to a vast amount of environmental influences including stress conditions which may cause harm to the stem cell preservation...
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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2022
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| Online Zugang: | PDF-Volltext |
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| Zusammenfassung: | Proper tissue homeostasis is often regulated and maintained by stem cells, which undergo self-renewal to furthermore produce differentiating daughter cells. Tissues are exposed to a vast amount of environmental influences including stress conditions which may cause harm to the stem cell preservation. In order to maintain homeostasis, cell lineages are subject to different tasks which also include strategies on stem cell replacement. An advantageous model organism for the study of stem cells in vivo is the insect organism Drosophila melanogaster. In particular, the Drosophila follicle stem cell lineage is a model example of stem cell based epithelial cell lineages due to the conservation of tissue organization and its easy accessibility. The lineage is located in the ovaries of female flies and contributes to crucial functions within oogenesis as it produces the epithelial coating of the developing oocyte. Recent studies demonstrated that cells independent of the follicle stem cell lineage in Drosophila may convert to stem cells upon environmental perturbation. When flies are exposed to food deprivation, specialized niche cells, known as escort cells, are equipped with the ability to convert to follicle stem cells. In the absence of food deprivation, overactivation of Toll signaling, a pathway responsible for embryonic development and immune activities in flies, can induce escort cell conversion. The conversion of differentiated cells to another differentiated cell type is referred to as transdifferentiation and in the context of escort cell conversion, this might depict a mechanism of stem cell recovery. Since starvation has been reported to induce escort cell conversion in Drosophila, this study seeks to identify more environmental stressors which could trigger these conversion events. Therefore, the follicle stem cell lineage in Drosophila has been used and flies were exposed to a number of environmental factors including water and protein starvation, exposure to the Bisphenol A chemical, mating restraint and high fat diet. In addition, with the usage of ribonucleic acid interference fly lines, Toll pathway knockdown flies were exposed to starvation in order to investigate whether the pathway controls the conversion event. To visualize the conversion, fly lines were utilized in which escort cell lineages could be traced in the tissue. This was achieved via an escort cell specific promoter in combination with a clonal marking system.
The environmental screen revealed that protein starvation and the exposure to Bisphenol A induces escort cell conversion, whereas several other conditions indicate the same trend. Additionally, in starved Toll knockdown flies, escort cell conversion increased compared to its control. I therefore reasoned that the Toll pathway is not necessary for escort cell conversion.
Guided by the discoveries of different escort cell subtypes, escort cells were furthermore examined specifically within this study. With the aspiration to identify these subpopulations and associated marker genes which could hence facilitate the application of novel tools for escort cell subtypes, an escort cell specific single cell sequencing dataset was analyzed and compared to published escort cell datasets. The analysis of the escort cell specific dataset showed that calculated marker genes were not present in the escort cell compartments, which led me to the conclusion that the dataset was mostly composed of cells other than escort cell origin.
Despite methodological difficulties such as driver strength or statistical sample size, this study produced significant results regarding the effect of environmental factors on escort cell conversion. I concluded that the conversion event is highly dependent on the exposure to distinct environmental conditions. Considering results from this and other studies, metabolism and the evolutionary conserved Target of Rapamycin pathway seem to be involved in this process. In this context, I postulate that strong environmental stressors lead to follicle stem cell loss or dedifferentiation as a consequence of metabolic disruption. Hence, cell fate switching of escort cells would depict a recovery strategy on stem cell loss. This study argues for the capability of escort cells to convert to follicle stem cells and therefore maintain tissue homeostasis of the Drosophila follicle epithelium. This underlines the versatile response of niches to their environment and provides us with a more detailed insight in niche and stem cell networks. |
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| Umfang: | 163 Seiten |
| DOI: | 10.17192/z2023.0131 |