Analysis of cell fate choice regulation in organiser/primitive streak stem cells and neuroectoderm progenitors.

组织者/原条干细胞和神经外胚层祖细胞的细胞命运选择调节分析。

• 批准号: G1002174/1
• 负责人: Jacqueline Dale
• 金额: $ 76.01万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002174%2F1
• 关键词: Analysis; cell; fate; choice; regulation

The body axis, backbone and spinal cord are formed very early in development; during the first month of pregnancy in humans, between days 8 and 12 of development in the mouse and between days 1 and 4 in the chick. These structures form from a group of cells called axial progenitors that are similar to stem cells. Stem cells have two essential properties: they can divide to give more copies of themselves and they can produce a variety of specialised cell types in a process called differentiation. Disruption to the genes that regulate the functions of these particular progenitor cells, in animal models or human pathologies, causes a loss of axial tissue development, loss of patterning of the spinal cord, and can lead to severe holoprosencephaly or lethality of embryos. These tissues and processes are thus of fundamental importance to the developing embryo and a detailed understanding of how they develop and the molecules mediating their respective functions is crucial both to the understanding of embryo development and the generation of means of treating embryonic defects. It is vitally important for the developing embryo that the right number of these axial progenitor cells chooses to differentiate into each of the specialised cell types so that the embryo develops into the right size and shape. We aim to understand what molecules make these cells choose which cell type to differentiate into. To date, very little was known about what regulates the cell fate choice of these particular stem cell-like progenitors. We have recently identified a key molecular pathway regulating this event and we plan to investigate the biochemical basis of this regulation.In mice, unlike Embryonic Stem cells, these cells do not form malignant tumours when transplanted into adults and may therefore become a useful therapeutic cell type for degenerative diseases and injuries involving the spinal cord, and the back bone.

体轴、脊柱和脊髓在发育的早期形成;人类在怀孕的第一个月，小鼠在发育的第8天至第12天，小鸡在发育的第1天至第4天。这些结构由一组称为轴向祖细胞的细胞形成，它们与干细胞相似。干细胞有两个基本特性：它们可以分裂以产生更多的自身拷贝，并且它们可以在称为分化的过程中产生各种专门的细胞类型。在动物模型或人类病理学中，对调节这些特定祖细胞功能的基因的破坏会导致轴向组织发育的丧失、脊髓图案的丧失，并可能导致严重的前脑无裂畸形或胚胎的致死性。因此，这些组织和过程对于发育中的胚胎具有根本重要性，并且详细了解它们如何发育以及介导它们各自功能的分子对于理解胚胎发育和产生治疗胚胎缺陷的方法都是至关重要的。对于发育中的胚胎至关重要的是，这些轴向祖细胞的正确数量选择分化成每种专门的细胞类型，以便胚胎发育成正确的大小和形状。我们的目标是了解是什么分子使这些细胞选择分化成哪种细胞类型。到目前为止，人们对是什么调节这些特定干细胞样祖细胞的细胞命运选择知之甚少。我们最近已经确定了一个关键的分子途径调节这一事件，我们计划调查这种调节的生化基础。在小鼠中，不像胚胎干细胞，这些细胞不会形成恶性肿瘤时，移植到成年人，因此可能成为一个有用的治疗细胞类型的退行性疾病和损伤，涉及脊髓和脊椎骨。