The use of CRISPR-scaring and single cell approaches to study mammary epithelial cell differentiation dynamics in health and disease

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Each organ in our body is composed of millions of cells. However, not all the cells within an organ are the same, they all have a defined role and fate which cumulatively dictates the function of the organ. The mammary gland is one of the defining organs that distinguishes mammals from other organisms. The primary role of the mammary gland is to produce and secrete milk to nurture new-born mammals. Just like any other organ the mammary gland is composed of multiple cell types each with a defined role and fate. Understanding how these different cell types relate to each other and contribute to development of disease is required. It is only within the last 5 years has it become technically feasible to identify which genes are active within a single cell. We have recently used this novel technology to profile 23,000 individual mammary cells and determine their identity and chart their fate. We found that we can divide the 23,000 cells in to 15 different groups based on their identity. We also found that there is a hierarchical structure to these 15 different groups of cells. Some groups were only found during milk production (lactation) while other cells were found in all stages and are capable of giving rise to most of the other types of cells. We call these cells progenitor cells. Further, we found that these progenitors maintain a "memory" of having undergone pregnancy which possibly facilitates milk production in subsequent pregnancy. Interestingly, it is known that an early pregnancy substantially decreases a woman's risk to develop breast cancer during her life. In this proposed study we aim to build on the identification of these different groups of cells and utilise the single cell technology to further understand the changes in the progenitor population in response to ageing, pregnancy and its role in cancer development.