Regulation of trophoblast stem cell homeostasis and differentiation by atypical protein kinase-C isoforms

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The placenta is a fetal organ that only exists during pregnancy. It is essential for fetal development, but little is known about the stem cells that form the human placenta. Trophoblasts are placental specific cells. The trophoblast stem cell forms all of the different types of trophoblasts that make up the placenta by changing, or differentiating, into other trophoblast cell types. These cells perform all the major functions of the placenta: they exchange nutrients and waste between the mother and the developing fetus, protect the fetus from the maternal immune system, secrete hormones, and invade the mother's uterus to help it change to support fetal development. The human trophoblast stem cell was only discovered in 2018. Therefore, extremely little is known about what controls human trophoblast stem cell differentiation. Our research program seeks to understand what controls human trophoblast stem cell differentiation. We are particularly interested in the role of  a group of proteins, the atypical protein kinase-c proteins, and how they may control human trophoblast stem cell differentiation. We propose to use different tissue culture models of human trophoblast stem cells to examine how atypical protein kinase-c proteins control human trophoblast differentiation. We will use different tools, such as pharmacologic inhibitors, genetic interference, and mutant forms of atypical protein kinase-c to see how changing the activity or abundance of atypical protein kinase c's changes trophoblast differentiation. This will create new knowledge about an important step of human development that is presently nearly completely unknown. This will be important knowledge for researchers examining the regulation of human development and placental development. It will also be important knowledge for researchers interested interested in understanding how development may be different between species.