Decoding cell lineages in human oesophagus, stomach and duodenal development for the Human Cell Atlas and to understand disease

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The purpose of this project is to discover which genes are switched on or switched off in the developing upper intestine and stomach in individual cells and to compare this information to adult tissue. In parallel we will discover which bits of the surrounding genome are active in controlling how the genes are switched on or off. We need to do this in individual cells because these tissues are very complex and made up of many different types of cell. The approach is important because the first step from normal gullet to disease is a change to something called 'Barrett's oesophagus'. In turn Barrett's oesophagus is presumed to be a step on the way to oesophageal cancer, which all too frequently is very aggressive and incurable. Previously, we have thought that Barrett's oesophagus is a switch from one adult type of cell to another. Recently, we have shown that the switch looks more like a reversion to a primitive embryonic state. The same is true of oesophageal cancer. This makes detailed understanding of normal development very important.We will generate datasets at different points in development so that we can understand the changes that occur over time at genome-scale using computational methods. We will ensure all the information is compatible with the requirements of the Human Cell Atlas so that we can share all our information freely and, in turn, benefit from data from other teams of researchers.