Transcription factor stoichiometry defines distinct pluripotent states

在人类发育过程中，细胞的行为就像积木一样，以一种有组织、有控制的方式奇妙地聚集在一起，形成了人体。在这个过程中，我们可以把细胞看作是由复杂的蛋白质相互作用组成的支撑基础组成的积木。这些支持基础决定了一个细胞是成为血液细胞、大脑细胞、皮肤细胞，还是构成人体的许多其他细胞类型。最早可以分离、培养和研究的细胞类型是胚胎干细胞。有趣的是，我们现在可以将成人细胞转化为与胚胎干细胞非常相似的细胞。这个过程被称为“重编程”，需要添加某些因素。增加这些因子的水平会产生一种独特的细胞类型，仅在分化潜力方面类似于胚胎干细胞。然而，这两种细胞类型在支持胚胎干细胞身份的蛋白质相互作用方面完全不同。拟议的研究旨在了解这两种细胞类型之间的相似之处。它还旨在确定蛋白质水平改变如何导致影响早期胚胎发育的蛋白质相互作用差异的新机制。具体来说，我们的目标是解决构建正常胚胎细胞背后的重要因素，最终导致正常发育。我们相信，我们的工作将为我们身体早期细胞决定健康的人类胚胎发育提供新的见解。

During human development, cells behave like building blocks and fascinatingly come together in an organized and well-controlled manner to build the human body. Within this process, we can think of cells as building blocks consisting of support foundations made up of complex protein interactions. These support foundations determine the choices of whether a cell becomes a blood, brain, or skin cell, or many other cell types that make up a human being. The earliest cell type that can be isolated, grown and studied is an embryonic stem cell. Interestingly, we can now convert adult cell into cells that highly resemble embryonic stem cells. This process, which is called “reprogramming”, requires the addition of certain factors. Increasing the levels of these factors gives rise to a unique cell type that resembles embryonic stem cells only in terms of differentiation potential. However, the two cell types completely differ in protein interactions that support the identity of embryonic stem cells. The proposed research aims on understanding the parallels between these two cell types. It also aims to identify new mechanisms of how altered protein levels lead to differences in protein interactions that can affect early embryo development. Specifically, we aim to resolve the important elements behind building a normal embryonic cell, which ultimately leads to normal development. We believe that our work will provide novel insights into the decisions taken by early cells of our body leading towards healthy human embryo development.