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

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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.