Investigating the processes and mechanisms of cellular decision-making

本项目旨在研究哺乳动物发育过程中细胞决策的过程和机制，重点关注细胞在胚胎中做出的第一个决定-神经外胚层和中胚层之间的命运。这个决定可以在小鼠胚胎干细胞（mESCs）中建模，这为探索这个决定提供了一个合适的基础，开辟了许多实验和理论途径。主要的方法将是利用单细胞技术的最新发展，通过分析单细胞RNA-seq数据来探索和描述潜在的遗传程序。这个项目有几个目标：(1)调查公开可用的数据来源，并将数据整理到一个数据库中，以便在可能的情况下进行荟萃分析(2)确定神经外胚层命运是否可以被认为是“主要的”，即在决定分化之前，细胞中是否存在神经命运的“转录组特征”。这将在Rue & Martinez Arias， 2015年所描述的“命运种族”的背景下进行考虑。(3)研究“准电位景观”框架的扩展，以概念化和描述涉及这一决定的复杂多能性和分化回路的行为。(4)初步分析后认为有必要，生成中胚层分化轨迹数据。在使用单细胞转录组学方法检测和表征细胞群体方面取得了很大的成功；然而。在研究细胞表达谱的功能特性方面进展较少。

This project aims to investigate the processes and mechanisms of cellular decision-making in the context of mammalian development, with a focus on the first decision that cells make in the embryo - between neuroectodermal and mesodermal fates. This decision can be modelled in mouse embryonic stem cells (mESCs) which open a number of experimental and theoretical avenues that provide a suitable substrate for exploring this decision. The primary approach will be to capitalise on the recent developments in single-cell technologies by analysing single-cell RNA-seq data in order to explore and describe the underlying genetic programs. There are several goals within this project: (1) Investigate publically-available sources of data and collate the data into a single database to enable meta-analysis, where possible (2) Identify whether the neuroectodermal fate can be considered 'primary', that is there a 'transcriptomic signature' of neural fate present in cells before the decision to differentiate. This will be considered in the context of 'fate races' as described in Rue & Martinez Arias, 2015.(3) Investigate extensions of the 'quasi-potential landscape' framework to conceptualise and describe the behaviour of the complex pluripotency and differentiation circuits implicated in this decision.(4) Generate data of the mesodermal differentiation trajectory if, after initial analysis, it is deemed necessary.There has been a great deal of success in using single cell transcriptomic methods to detect and characterise populations of cells; however. there has been less progress in the investigation of functional properties underlying a cell's expression profile.