PhD Student
Advisor: Mihaela Pavlicev

Unit for Theoretical Biology, Department of Evolutionary Biology
University of Vienna

Implantation is a key innovation of placental mammalian pregnancy. It coincides with the origin of a novel maternal cell type, the decidual stromal fibroblast. Under the influence of progesterone and prostaglandin E2 during pregnancy, these cells undergo a process known as decidualization. The resulting decidual tissue is necessary for successful implantation and pregnancy. The process of decidualization is highly similar to fibroblast activation- a response of fibroblasts to tissue perturbations, such as injury. Fibroblast activation entails transformation of the fibroblast to a myofibroblast, which leads to wound healing. Persistent fibroblast activation is a cause of excessive scarring (fibrosis).  In contrast, decidualization initially follows fibroblast activation, however it does not result either in wound healing nor in scarring, but in a distinct cell type - the decidual stromal cell. The hypothesis of this project is that decidualization coopted and modified fibroblast activation, by changing its later steps to accommodate implantation and embryo support. In order to address this, I am comparing already published single-cell RNA seq data of human endometrium across stages of the menstrual cycle, and data of the human skin at different stages of wound healing. As expected, the comparison of gene expression profiles between the two processes shows that the trajectory of fibroblast activation ends at the proliferative stage of wound healing and at the secretory stage in the endometrium, where the endometrial stromal cells are differentiating to pre-decidual stromal cells in the menstrual cycle. Inflammation appears to be a striking difference between the two processes - it is a key part of the fibroblast activation trajectory in wound healing, but not in decidualization. Downregulation of genes associated with inflammation may play a role in the modification of the process of fibroblast activation during the co-option by the process of decidualization.
Apart from the specific questions to do with describing modifications, this project addresses a fundamental evolutionary question: How do novel cell types evolve?