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，以一种有组织和良好控制的方式迷人地聚集在一起，构建人体。在这个过程中，我们可以认为细胞是由复杂的蛋白质相互作用组成的支持基础组成的积木。这些支持基础决定了细胞是成为血细胞、脑细胞还是皮肤细胞，还是构成人类的许多其他类型的细胞。可以分离、培养和研究的最早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高度相似的细胞。这一过程被称为“重新编程”，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，这种细胞类型只是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特性的蛋白质相互作用方面完全不同。这项拟议的研究旨在了解这两种细胞类型之间的相似之处。它还旨在确定新的机制，即蛋白质水平的变化如何导致蛋白质相互作用的差异，从而影响早期胚胎发育。具体地说，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做出的决定提供新的见解，从而导致人类胚胎的健康发展。

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.