Challenging key concepts in neural differentiation: the role of neuromesodermal progenitors in patterning the head-to-tail axis in vertebrates

神经分化中具有挑战性的关键概念：神经中胚层祖细胞在脊椎动物头尾轴模式中的作用

• 批准号: 2117385
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2117385
• 关键词: Challenging; key; concepts; neural; differentiation

In this project, this question will be investigated both in vitro in mouse pluripotent cells, and in two in vivo systems, mouse and chick embryos. NMPs are characterised by the coexpression of two transcription factors, T(brachyury) and Sox2. Meanwhile Sox1 expression characterises the site of future brain formation. Since we have fluorescent markers of these populations, this is a tractable in vitro system to follow the sequence of cell fate decisions needed to make brain and spinal cord at the single cell level. Analysis of single cell transcriptomes in parallel with analysis of their commitment will further characterise these cell fate decisions. Furthermore, in vitro culture of manipulated early mouse and embryos where future brain and spinal cord tissue are challenged by transplantation to spinal cord or brain environments respectively will test at what stage these cells are committed to brain or spinal cord fates: before or after their commitment to a neural identity. Our preliminary data suggests a rather similar sequence of events in each organism, but subtle differences in the generation of these anterior and posterior cell types may underpin some of the species differences; this will be analysed by comparison of chick and mouse transcriptomes.This project therefore challenges a fundamental concept in developmental biology, but also is likely to lead to improvements in the in vitro differentiation of pluripotent cells into cell types of clinical interest for degenerative disease and/or injury.

在这个项目中，这个问题将在小鼠多能细胞的体外和两个体内系统--小鼠和鸡的胚胎中进行研究。NMP的特征是两个转录因子T(Brachyury)和Sox2共表达。同时，Sox1的表达是未来大脑形成的特征。由于我们有这些种群的荧光标记，这是一个易于处理的体外系统，可以跟踪在单细胞水平上做出大脑和脊髓所需的细胞命运决定的序列。对单细胞转录本的分析与对它们的承诺的分析将进一步表征这些细胞的命运决定。此外，将未来的大脑和脊髓组织分别移植到脊髓或脑环境中挑战未来大脑和脊髓组织的操纵早期小鼠和胚胎的体外培养，将测试这些细胞在哪个阶段致力于大脑或脊髓的命运：承诺神经身份之前还是之后。我们的初步数据表明，每个生物体中发生的事件序列相当相似，但这些前部和后部细胞类型产生的细微差异可能是一些物种差异的基础；这将通过比较鸡和老鼠的转录本进行分析。因此，该项目挑战了发育生物学的基本概念，但也可能导致多能细胞体外分化为临床上对退行性疾病和/或损伤感兴趣的细胞类型的改进。