Charting cellular changes in the human breast associated with embryogenesis, parity, age, menopause and germline mutations

我们身体的每个器官都是由数百万个细胞组成的。然而，一个器官内的所有细胞并不都是相同的，它们都有一个明确的角色和命运，这累积地决定了器官的功能。乳腺是哺乳动物区别于其他生物的决定性器官之一。乳腺的主要作用是产生和分泌乳汁，以哺育新生的哺乳动物。就像任何其他器官一样，乳腺由多种类型的细胞组成，每种类型的细胞都有明确的角色和命运。需要了解这些不同类型的细胞如何相互关联并促进疾病的发展。只有在最近5年内，识别单个细胞内哪些基因是活跃的才变得在技术上可行。我们最近使用这项新技术分析了23,000个单独的小鼠乳腺细胞，并确定了它们的身份并绘制了它们的命运图。我们发现，我们可以根据细胞的身份将23,000个细胞分成15个不同的组。基于这项成功的研究，我们建议在这里使用相同的技术来研究人类乳腺细胞。我们的目标是分析从不同女性身上分离出来的细胞，以捕捉由年龄、哺乳期、更年期和BRCA1/2等基因突变引起的乳房组织变化。这将是有用的信息，因为众所周知，患乳腺癌的风险随着年龄增加而降低。因此，我们研究的数据将阐明与这些不同的乳腺癌风险调节因子相关的细胞变化。

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 mouse 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. Based on this successful study we propose here to use the same technology to study human breast cells. We aim to analyse cells isolated from different women with a view of capturing changes in the breast tissue mediated by age, lactation, menopause and genetic mutations such as Brca1/2. This is will be useful information as it is known that the risk of developing breast cancer is increased with age and reduced with pregnancy. Therefore, data from our study will shed light on the cellular changes associated with these different breast cancer risk modulators