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

该项目的目的是发现在单个细胞中发育中的上肠和胃中哪些基因被打开或关闭，并将这些信息与成人组织进行比较。与此同时，我们将发现周围基因组的哪些部分在控制基因如何打开或关闭方面发挥作用。我们需要在单个细胞中这样做，因为这些组织非常复杂，由许多不同类型的细胞组成。这种方法很重要，因为从正常食道到疾病的第一步是改变为所谓的“巴雷特食管”。反过来，巴雷特食管被认为是通往食管癌的一步，而食管癌通常是非常具有侵略性和不可治愈的。以前，我们认为巴雷特食管是从一种成年细胞类型转换到另一种类型。最近，我们已经表明，开关看起来更像是一个原始胚胎状态的逆转。食管癌也是如此。这使得对正常发育的详细了解变得非常重要。我们将在发育的不同阶段生成数据集，以便我们可以使用计算方法在基因组尺度上了解随时间发生的变化。我们将确保所有的信息都符合人类细胞图谱的要求，这样我们就可以自由地分享我们的所有信息，并从其他研究团队的数据中受益。

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.