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

胎盘是只在怀孕期间存在的胎儿器官。它对胎儿发育至关重要，但人们对形成人类胎盘的干细胞知之甚少。滋养细胞是胎盘特异性细胞。滋养细胞干细胞通过改变或分化成其他类型的滋养细胞，形成构成胎盘的所有不同类型的滋养细胞。这些细胞执行胎盘的所有主要功能：它们在母体和发育中的胎儿之间交换营养和废物，保护胎儿免受母体免疫系统的侵害，分泌激素，并侵入母体子宫以帮助其改变以支持胎儿发育。人类滋养细胞干细胞直到2018年才被发现。因此，对控制人类滋养细胞干细胞分化的因素知之甚少。我们的研究项目旨在了解控制人类滋养细胞干细胞分化的因素。我们对一组蛋白质的作用特别感兴趣，非典型蛋白激酶-c蛋白，以及它们如何控制人类滋养细胞干细胞分化。我们建议使用不同的人滋养细胞干细胞组织培养模型来研究非典型蛋白激酶-c蛋白如何控制人滋养细胞分化。我们将使用不同的工具，如药物抑制剂、遗传干扰和非典型蛋白激酶c的突变形式，以观察改变非典型蛋白激酶c的活性或丰度如何改变滋养细胞分化。这将为目前几乎完全未知的人类发展的一个重要步骤创造新的知识。这对于研究人类发育和胎盘发育调控的研究人员来说将是重要的知识。对于想要了解物种之间的发育差异的研究人员来说，这也将是重要的知识。

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.