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Investigating the processes and mechanisms of cellular decision-making

研究细胞决策的过程和机制

基本信息

批准号：
1645696
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1645696
关键词：
Investigating processes mechanisms cellular decision

项目摘要

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.

该项目旨在研究哺乳动物发育背景下细胞决策的过程和机制，重点是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。这一决定可以在小鼠胚胎干细胞(MESCs)中模拟，这开辟了许多实验和理论途径，为探索这一决定提供了合适的底物。主要的方法将是通过分析单细胞RNA序列数据来利用单细胞技术的最新发展，以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单一的数据库中，以便在可能的情况下进行荟萃分析；(2)确定神经外胚层的命运是否可以被认为是“主要的”，即在决定分化之前，细胞中存在神经命运的“转录切割签名”。这将在Rue&Martinez Arias，2015所描述的‘命运竞赛’的背景下被考虑。(3)研究‘准潜力格局’框架的扩展，以概念化和描述这一决定所涉及的复杂的多能性和分化回路的行为。(4)如果在初步分析后认为有必要，生成中胚层分化轨迹的数据。在使用单细胞转录方法来检测和表征细胞群体方面已经取得了巨大的成功；然而。在研究细胞表达谱的功能特性方面进展较少。