Investigating the role of Lin28A in human embryonic neural lineage function

集中于神经系统早期发育的研究通常利用小鼠模型。虽然这项工作为神经系统中的细胞如何形成提供了巨大的见解，但与人类神经发育的直接相关性并不总是清楚的。在这项计划中，我们将使用最不成熟的人类细胞，胚胎干细胞，来了解神经发育过程中最早的变化，包括不同类型的神经细胞如何形成，神经细胞如何生长，它们如何具有干细胞特性以及它们如何移动。我们最近发现了人类胚胎干细胞的特征，这些细胞生长非常迅速，不能正常发育成不同的神经细胞类型。通过将这些变异的人类胚胎神经细胞与正常的人类胚胎神经细胞进行比较，我们已经确定了一系列可能调节人类神经细胞生长和发育成更特定功能细胞类型之间平衡的基因。我们将测试其中一个基因Lin28A如何直接调节这些早期神经过程之间的平衡。确定基因如何控制这种平衡对于更好地理解我们神经系统的基本形成以及微小的表达变化如何导致非常不同的结果至关重要。

Studies focusing on the early development of the nervous system typically utilize mouse models. While this work has provided tremendous insight into how the cells in the nervous system are formed, the direct relevance to human neural development is not always clear. In this proposal, we will be using the most immature human cells, embryonic stem cells, to understand the earliest changes during neural development including how different types of neural cells form, how neural cells grow, how they take on stem cell properties and how they move. We have recently characterized human embryonic stem cells that grow very rapidly and do not properly develop into different neural cell types. By comparing these variant human embryonic neural cells to normal human embryonic neural cells, we have identified a list of genes that may regulate the balance between human neural cell growth and development into more specific functional cell types. We will test how one of these genes, Lin28A, directly regulates the balance between these early neural processes. Identifying how genes control this balance will be critical in an attempt to gain a better understanding of the basic formation of our nervous system and how small expression changes can give rise to very different outcomes.