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

非典型蛋白激酶-C 亚型对滋养层干细胞稳态和分化的调节

• 批准号: RGPIN-2021-02807
• 负责人: Riddell, Meghan
• 金额: $ 2.19万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761556
• 关键词: Regulation; trophoblast; stem; cell; homeostasis

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.

胎盘是一种胎儿器官，只存在于怀孕期间。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。滋养层细胞是胎盘特异性细胞。滋养层干细胞通过改变或分化成其他滋养层细胞类型形成构成胎盘的所有不同类型的滋养层。这些细胞执行胎盘的所有主要功能：它们在母亲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影响，分泌激素，并侵入母亲的子宫以帮助其改变以支持胎儿发育。人类滋养层干细胞直到2018年才被发现。因此，很少有人知道是什么控制人类滋养层干细胞分化。我们的研究计划旨在了解是什么控制人类滋养层干细胞分化。我们特别感兴趣的是一组蛋白质的作用，非典型蛋白激酶-c蛋白，以及它们如何控制人类滋养层干细胞分化。我们建议使用不同的人滋养层干细胞的组织培养模型，以研究非典型蛋白激酶-c蛋白如何控制人滋养层分化。我们将使用不同的工具，如药理学抑制剂，遗传干扰和非典型蛋白激酶c的突变形式，看看如何改变非典型蛋白激酶c的活性或丰度改变滋养层分化。这将创造关于人类发展的一个重要步骤的新知识，而这一步骤目前几乎完全未知。这将是研究人类发育和胎盘发育调节的重要知识。对于有兴趣了解物种之间发育差异的研究人员来说，这也是重要的知识。