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基于人类iPSC的乳腺癌模型识别了由BRCA1突变诱导的S100P依赖的癌症干

Jingxin Liu^{1,2,3,4,5,6,7}, Cai Zhao^1,2,3,4,7,8, Jiahao Chen^1,2,3,4,5,7

¹Department of Rehabilitation Medicine, The Seventh Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.

Science advances

|July 25, 2025

概括

研究人员开发了一种新的人类干细胞模型来研究乳腺癌的发展. 该模型使用诱导多能干细胞 (iPSC),模仿患者的瘤,并将S100P确定为乳腺癌的关键驱动因素.

科学领域:

生物医学研究的研究.
干细胞生物学干细胞生物学
在瘤学瘤学.

背景情况:

乳腺癌是全球妇女死亡的主要原因.
了解乳腺癌的发展受到缺乏准确的人类模型的阻碍.
生殖系BRCA1突变显著增加乳腺癌的风险.

研究的目的:

开发一种人体体外试验模型,用于研究乳腺癌的发病和进展.
为了研究BRCA1突变在乳腺瘤发生中的作用.
为了确定与BRCA1相关的乳腺癌的新型治疗点.

主要方法:

从人类诱导的多能干细胞 (iPSC) 产生功能性乳腺样细胞 (MCs).
开发一种乳腺癌模型,使用患有生殖系BRCA1突变的患者衍生的iPSCs.
对iPSC衍生细胞和患者衍生乳腺癌细胞的转录和基因组分析.
功能性测试以评估瘤发生潜力和癌症干性.

主要成果:

从细胞,转录和功能方面来看,iPSC衍生的MCs与人类初级MCs非常相似.
来自患者的iPSC-MC模型准确地回顾了乳腺癌转录组和基因组变化.
确定S100P是突变BRCA1的下游瘤基因,促进癌症干和瘤发生.
证明了患者衍生的iPSC-MCs的瘤发生潜力.

结论:

为乳腺癌研究建立了一个强大的基于人类干细胞的模型.
提供了对BRCA1突变乳腺癌分子机制的见解.
确定S100P作为乳腺癌治疗的潜在治疗标.

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