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

使用 CRISPR 惊吓和单细胞方法研究健康和疾病中乳腺上皮细胞分化动态

基本信息

批准号：
BB/S006745/1
负责人：
Walid Khaled
金额：
$ 66.62万
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：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS006745%2F1
关键词：
use CRISPR scaring single cell

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 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.

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。我们最近使用这项新技术对23，000个个体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。我们还发现，这15组不同的细胞有一个层次结构。有些细胞群只在产奶（哺乳）期间发现，而其他细胞则在所有阶段都能发现，并且能够产生大多数其他类型的细胞。我们称这些细胞为祖细胞。此外，我们发现，这些祖细胞保持了一种“记忆”，经历了怀孕，这可能有助于在随后的怀孕产奶。有趣的是，众所周知，早孕大大降低了妇女一生中患乳腺癌的风险。在这项拟议的研究中，我们的目标是建立在这些不同细胞群的鉴定基础上，并利用单细胞技术进一步了解祖细胞群体对衰老、妊娠及其在癌症发展中的作用的反应。

项目成果

期刊论文数量（10）

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

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

Brca1 相关乳腺肿瘤发生的时间分辨单细胞分析揭示腔祖细胞的异常分化