Speaker: Kelby Kies, graduate student in the Tuteja Lab

Title: "Identifying novel regulators of uterine function during pregnancy"

Abstract: To support embryonic growth and placenta development during early pregnancy, the endometrium, which is the tissue lining the inside of the uterus, must morphologically and functionally transform into the decidua through multiple processes including the differentiation of endometrial stromal cells (ESC) into decidual stromal cells (DSC), angiogenesis, remodeling of the extracellular matrix (ECM), and recruitment of immune cells. These biological processes are collectively referred to as the decidualization of the endometrium. If any of these processes are compromised, pregnancy complications can occur. Individual genes underlying each process have been identified, however, the protein protein interaction (PPI) networks have not been defined. Understanding the PPI networks regulating decidualization of the endometrium is an important step towards understanding the origin of early pregnancy complications. 

To study the processes involved in the decidualization of the endometrium, we obtained the mouse decidua at two critical timepoints during early pregnancy, embryonic day e7.5 and e9.5. By e7.5, the decidua has attained maximum thickness through the differentiation of endometrial stromal cells (ESC) into decidual stromal cells (DSC), the most abundant cell type of the decidua. DSC play a variety of essential roles in the processes involved in the decidualization of the endometrium. Based on this, we expected that e7.5 is critical for understanding the key processes that occur during this phase of decidualization. As pregnancy progresses, the decidual vasculature continues to rapidly develop, through angiogenesis, to provide sufficient blood flow to the placenta. E9.5 is the final timepoint before blood flow to the placenta is established.

To investigate the molecular mechanisms underlying these two essential processes, we generated bulk RNA-seq data and performed differential expression analysis between e7.5 and e9.5 to identify differentially expressed genes (DEGs) within the tissue. Protein-protein interaction (PPI) networks were constructed for each timepoint based on the identified DEGs. To pinpoint the active enhancer regions and transcription factors (TFs) regulating these networks, we generated H3K27Ac ChIP-seq data from the mouse decidua at the same timepoints. Additionally, we utilized publicly available single-cell RNA-seq data from human decidua to deconvolute the networks into the maternal cell types involved in endometrial decidualization. The insights gained from this study will advance the understanding of the complex biological processes occurring during decidualization.