对复制应激的转录反应选择性地扩大了Brca2-突变乳腺上皮细胞的子集
Maryam Ghaderi Najafabadi1, G Kenneth Gray2, Li Ren Kong3,4,5,6
1Department of Oncology, University of Cambridge, Cambridge, UK.
Nature communications
|August 25, 2023
概括
乳腺癌细胞中的BRCA2突变引发了对复制应激的反应,扩大了荷尔蒙受体负光细胞. 这种扩张与Tspan8和Thrsp等特定基因有关.
科学领域:
- 遗传学 是一个遗传学.
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
背景情况:
- 生殖线BRCA2突变与光线乳腺癌有关.
- 对于BRCA2突变对乳腺上皮亚群的影响尚不清楚.
研究的目的:
- 研究BRCA2突变如何在复制压力下影响乳腺上皮亚群.
主要方法:
- 使用来自单基因Brca2突变小鼠的乳腺器官.
- 应用于对有机体的复制应力.
- 进行了CyTOF和scRNA-seq分析.
- 使用CRISPR/Cas9来删除特定的基因 (Tspan8,Thrsp).
主要成果:
- 单基Brca2突变导致在复制压力下荷尔蒙受体阴性 (HR-) 光细胞的选择性扩张.
- Brca2突变HR-光细胞显示有机体形成,生存和扩张的增加.
- 扩大的HR-光细胞表达高的Tspan8,Thrsp和I型干扰素反应通路.
- 删除Tspan8或Thrsp会抑制Brca2突变HR-光细胞的扩张.
结论:
- BRCA2突变诱导对复制应激的转录反应,有利于HR-光细胞的外生长.
- Tspan8和Thrsp是这种扩张的关键媒介,可能通过干扰素反应和乳腺膜基因通路.
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