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

绘制人类乳房中与胚胎发生、胎次、年龄、更年期和种系突变相关的细胞变化

基本信息

批准号：
MR/S036059/1
负责人：
Walid Khaled
金额：
$ 60.31万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FS036059%2F1
关键词：
Charting cellular changes human breast

项目摘要

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

我们身体的每个器官都是由数百万个细胞组成的。然而，并不是器官内的所有细胞都是相同的，它们都有一个明确的角色和命运，累积决定了器官的功能。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养育新生哺乳动物。就像任何其他器官一样，乳腺由多种细胞类型组成，每种细胞都有明确的作用和命运。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。在过去的5年中，技术上已经可以识别出单个细胞中哪些基因是活跃的。我们最近使用这种新技术对23，000个小鼠乳腺细胞进行了分析，并确定了它们的身份并绘制了它们的命运。我们发现，我们可以根据它们的身份将23，000个细胞分为15个不同的组。基于这项成功的研究，我们在这里建议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中分离的细胞，以捕获由年龄，哺乳，绝经和基因突变（如Brca 1/2）介导的乳腺组织变化。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的增长而增加，随着怀孕而减少。因此，我们的研究数据将揭示与这些不同乳腺癌风险调节剂相关的细胞变化

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors.

DOI：
10.1038/s41467-021-21783-3
发表时间：
2021-03-09
期刊：
Nature communications
影响因子：
16.6
作者：
Bach K;Pensa S;Zarocsinceva M;Kania K;Stockis J;Pinaud S;Lazarus KA;Shehata M;Simões BM;Greenhalgh AR;Howell SJ;Clarke RB;Caldas C;Halim TYF;Marioni JC;Khaled WT
通讯作者：
Khaled WT

Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk.

乳腺过程中乳腺的转录变化显示，通过人牛奶的细胞单细胞测序揭示了。

DOI：
10.1038/s41467-021-27895-0
发表时间：
2022-01-28
期刊：
Nature communications
影响因子：
16.6
作者：
Twigger AJ;Engelbrecht LK;Bach K;Schultz-Pernice I;Pensa S;Stenning J;Petricca S;Scheel CH;Khaled WT
通讯作者：
Khaled WT

Mammary gland development from a single cell 'omics view.