The induction of PGCs from pluripotent cells in axolotl embryos

蝾螈胚胎中多能细胞诱导 PGC

• 批准号: G0700078/1
• 负责人: Andrew Johnson
• 金额: $ 31.85万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700078%2F1
• 关键词: induction; PGCs; pluripotent; cells; axolotl

During normal animal development the cells that are egg and sperm come from cells called primordial germ cells, or PGCs. Little is known about how PGCs form in humans, but this is very important, because it can help with fertility problems, and with understanding the origins of ovarian and testicular tumors. Also, PGCs come from precursor cells that are pluripotent, which means they can become any other cell in the body. In this way PGCs are very similar to embryonic stem cells, or ES cells. Understanding how ES cells form, and retain their capacity for becoming other cells, is a major goal of modern biomedical science. A fundamental approach to modern developmental biology is to study how cells behave in the embryos of less advanced animals, then transfer knowledge from these studies to understand how similar processes are controlled in mammals, and ultimately humans. This approach is useful because the embryos of lower animals are usually much larger and easy to manipulate, and so experiments are less expensive and easier to perform. Also, this approach minimizes the distress that more advanced animals might encounter. Many scientists use embryos from frogs or from fish, but the species usually used form PGCs through a mechanism that is not relevant to humans. We developed axolotl embryos as model experimental system because it produces PGCs in a manner very similar to humans. As proof of this we have previously cloned genes from this species that are known to be required in human pluripotent cells. Using embryos from axolotls has allowed us to understand how pluripotent cells are produced in normal embryos, and how they are governed during development. In this work we prove for the first time that PGCs can be induced in vast numbers, in a highly enriched form, using very simple methods that we developed. Here we are working to further validate and refine our methods, and to understand the actual genes and mechanisms that are involved in PGCs formation. This system will make PGCs useful as novel tools to understand how pluripotency is controlled. Also, this work will be very important in aiding our understanding of how stem cells develop in embryos, and how germ cells are made distinct from other types of cells in the body.

在正常的动物发育过程中，卵子和精子细胞来自原始生殖细胞，或PGCs。关于PGCs如何在人类中形成的知之甚少，但这非常重要，因为它可以帮助解决生育问题，并了解卵巢和睾丸肿瘤的起源。此外，PGCs来自多能性的前体细胞，这意味着它们可以成为体内的任何其他细胞。在这方面，PGCs与胚胎干细胞或ES细胞非常相似。了解胚胎干细胞是如何形成的，并保持它们成为其他细胞的能力，是现代生物医学科学的一个主要目标。现代发育生物学的一个基本方法是研究细胞在较不发达动物的胚胎中的行为，然后将这些研究中的知识转移到哺乳动物中，并最终了解类似过程是如何控制人类的。这种方法很有用，因为低等动物的胚胎通常要大得多，容易操作，因此实验成本较低，更容易进行。此外，这种方法最大限度地减少了更先进的动物可能遇到的痛苦。许多科学家使用来自青蛙或鱼类的胚胎，但这些物种通常通过一种与人类无关的机制形成PGCs。我们开发了蝾螈胚胎作为模型实验系统，因为它以与人类非常相似的方式产生PGC。为了证明这一点，我们以前已经从这个物种中克隆了人类多能细胞所需的基因。使用蝾螈胚胎使我们能够了解多能细胞是如何在正常胚胎中产生的，以及它们在发育过程中是如何被控制的。 在这项工作中，我们第一次证明了PGC可以大量诱导，以高度富集的形式，使用我们开发的非常简单的方法。在这里，我们正在努力进一步验证和完善我们的方法，并了解参与PGC形成的实际基因和机制。该系统将使PGCs作为了解多能性是如何控制的新工具。此外，这项工作将非常重要，有助于我们了解干细胞如何在胚胎中发育，以及生殖细胞如何与体内其他类型的细胞区分开来。