The induction of PGCs from pluripotent cells in axolotl embryos

在正常的动物发育过程中，卵子和精子细胞来自称为原始生殖细胞或PGC的细胞。关于PGCs在人类中是如何形成的，人们知之甚少，但这一点非常重要，因为它可以帮助解决生育问题，并有助于了解卵巢和睾丸肿瘤的起源。此外，PGCs来自多能的前体细胞，这意味着它们可以成为体内的任何其他细胞。在这种情况下，PGCs与胚胎干细胞或ES细胞非常相似。了解ES细胞如何形成并保持其成为其他细胞的能力，是现代生物医学科学的主要目标。现代发育生物学的一个基本方法是研究细胞在不太发达的动物的胚胎中的行为，然后从这些研究中转移知识，以了解类似的过程在哺乳动物中是如何控制的，最终是在人类身上。这种方法很有用，因为低等动物的胚胎通常要大得多，易于操作，因此实验成本更低，更容易进行。此外，这种方法将更高级的动物可能遇到的痛苦降至最低。许多科学家使用青蛙或鱼的胚胎，但这些物种通常通过一种与人类无关的机制形成原生殖细胞。我们开发了axolotl胚胎作为模型实验系统，因为它产生PGCs的方式与人类非常相似。作为这一点的证据，我们之前已经从这个物种克隆了已知人类多能细胞所需的基因。使用来自Axolotl的胚胎使我们能够理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管理的。在这项工作中，我们首次证明，使用我们开发的非常简单的方法，可以以高度丰富的形式大量诱导PGC。在这里，我们正在努力进一步验证和改进我们的方法，并了解参与PGCs形成的实际基因和机制。这一系统将使PGCs成为了解多能性是如何被控制的新工具。此外，这项工作将有助于我们理解干细胞是如何在胚胎中发育的，以及生殖细胞是如何与体内其他类型的细胞区分开来的。

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.