Placental mammals are one of the most successful groups of animals, with more than 4,000 species adapted in diverse environments from dissert to ocean. Among the possible factors which contributed to the current success of the group, arguably one of the most important ones is the evolution of placentation. Elucidating how this transition in the mode of reproduction occurred is one of the critical issues in the study of mammalian evolution. In this dissertation, I look at the evolution of placentation from a perspective of the evolution of uterine cell types which critically involve the process of placenta formation: endometrial stromal fibroblasts (ESF) and decidual stromal cells (DSC). Upon pregnancy, DSC differentiates from ESF, a precursor uterine cell type, and they are collectively called endometrial stromal cells (ESC). The process of cellular transformation of ESF into DSC is called decidualization, and it is essential for the successful implantation of embryos as well as the maintenance of pregnancy. The evolution of ESC is thought to be instrumental in the evolution of placentation and gene regulatory network governing its differentiation has been studied extensively in recent years. However, some important questions remained unanswered, and one of the critical issues was the evolutionary origin of ESC. The implications of gene regulatory network evolution in ESC change greatly depending on which cell type is a proper counterpart for comparison. Therefore, characterization of the evolutionary history of ESC can have a huge impact on our understanding of the evolution of ESC, and consequently the evolution of placentation.
Thus, in this dissertation, I aim at elucidating the evolutionary history of ESC from various angles. Followed by a review of existing literature on the evolution of placentation and decidualization, I explore and present a conceptual framework to study cell type evolution. Then, firstly, I looked at the relationship of ESC to other cell types in the human body using RNA-Seq data. The cell differentiation process creates historical relatedness among cell type transcriptomes, and the cell differentiation process in turn is expected to reflect the history of cell type evolution, according to the sister cell type model of cell type evolution, which assumes that new cell types arise initially as a duplicated pair of an ancestral cell type. Therefore, a phylogenetically reconstructed relationship of cell type transcriptomes is expected to reflect an evolutionary relationship of cell types. The reconstructed phylogeny of cell types shows that ESC is closely related to an immune cell type called follicular dendritic cells, which implies the evolutionary origin of ESC as an immune cell type. The biological relevance of this result was also shown by the disappearance of DSC molecular marker genes by knocking down transcription factors which are predicted through phylogenetic reconstruction to be functional in decidualization. Secondly, I tried to find a homologous cell type of ESF or DSC in the uterus of a marsupial, Monodelphis domestica. Through immunohistochemical studies using various molecular markers of ESF and DSC, I found a uterine cell population in M. domestica which expresses a set of transcription factors essential for ESF. This cell population never expressed genes known to be commonly expressed in DSC. This leads to the conclusion that marsupials possess a cell type homologous to ESF but not DSC, and that DSC evolved from ESF in the stem lineage of eutherian mammals. Finally, I investigated how the transcriptome of ESF evolved during the evolution of mammals in response to the changes in the mode of placentation by collecting RNA-Seq data from six mammalian species, opossum, cow, mink, rat, rabbit, and human. Ancestral reconstruction based on phylogeny revealed interesting differences between the transcriptomes of eutherian ESFs and opossum ESFs, which shows that eutherian ESFs should be regarded as "neo-ESF" as opposed to "paleo-ESFs" in marsupials.
|Advisor:||Wagner, Gunter P.|
|School Location:||United States -- Connecticut|
|Source:||DAI-B 76/11(E), Dissertation Abstracts International|
|Subjects:||Evolution and Development|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be