Decoding differentiation of cell lineages in the early human liver for application in stem cell differentiation and cell programming

不同类型的人类肝细胞，如肝细胞和胆管细胞，迫切需要大量用于再生医学和开发中的药物安全性测试。成年细胞很难获得，而且质量往往各不相同。肝癌细胞系异常。因此，极大的兴趣集中在将培养皿中的干细胞转化为肝细胞，或者通过将容易获得的细胞（例如皮肤细胞）直接重编程为特定类型的肝细胞。然而，尽管经过近20年的努力，我们这样做的能力仍然有限。我们认为，了解这些细胞在人类早期发育中是如何产生的是关键的缺失部分。最近的技术进步已经彻底改变了我们对人体器官如何组合的研究能力。我们将通过观察组织样本中的一些简单标志物，建立一个早期人类肝脏发育的所有步骤的框架。然后，我们将通过捕捉每一种细胞所开启的基因，来发现每一种细胞出现时的全部细节，我们已经证明，这种类型的工作，在使用复杂的计算机程序进行分析时，可以挑选出在每个细胞中起作用的最关键因素。然后，我们有一个独特的机会来测试干细胞和细胞重编程中的这些因子，看看它们是否能提高我们的能力，使肝细胞看起来更像真实的东西。一旦我们完成了我们的工作，我们将与世界各地的研究人员分享结果和原始数据，以便我们都能从我们的新知识中迅速受益。

The different types of human liver cell, such as hepatocytes and bile duct cells, are urgently needed in large quantities for regenerative medicine and for safety testing drugs in development. Adult cells are hard to come by and often vary in quality. Liver cancer cell lines are abnormal. Therefore, great interest has focused on turning stem cells in a dish into liver cells, or by reprogramming readily available cells (e.g. skin cells) directly into particular types of liver cell. However, despite nearly twenty years of trying our ability to do this is still limited. We think that knowing how these cells arise in early human development is the critical missing component. Recent advances in technology have revolutionised our ability to undertake these studies of how human organs are put together. We will build a framework of all the steps in how the early human liver developments by looking at some simple markers in tissue samples. We will then discover the full detail about the individual types of cell as they emerge by capturing every gene that they turn on. We have already shown that this type of work, when analysed using complex computer programmes, can pick out the most critical factors operating in each cell. We then have a distinctive opportunity to test these factors in stem cells and in cell reprogramming to see if they improve our ability to make liver cells that look more like the real thing. Once we have undertaken our work we will share both the results and the raw data with researchers around the world so that we can all benefit quickly from our new knowledge.