不同的染色质可访问性和转录动态定义了乳腺癌亚型及其血统
bioRxiv : the preprint server for biology
|November 14, 2023
概括
这项研究确定了乳腺癌亚型的特定细胞起源和基因网络. 研究人员将基因表达和染色质可访问性联系起来,以了解基础性和光线性乳腺癌的发展.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 乳腺癌是一种复杂的疾病,具有明显的分子亚型.
- 这些亚型的细胞起源和转录网络尚未完全理解.
研究的目的:
- 研究原始细胞和转录网络,定义基底类和光线性乳腺癌亚型.
- 在乳腺癌中建立基因表达,染色质可访问性和血统发展之间的联系.
主要方法:
- 应用多原子技术,包括散装,单细胞 (sc) 和单核 (sn) RNA-seq和ATAC-seq.
- 在61个患者样本上利用了PAM50亚型,轨迹分析,调节网络分析,空间转录组学和多重成像.
- 使用snATAC确认了促进子可访问性,并确定了关键的谱系定义基因.
主要成果:
- 乳腺癌亚型与它们的原始细胞之间在基因表达和染色质可访问性方面建立了特征性联系.
- 确定BHLHE40对光线乳腺癌至关重要,KLF5对基底类瘤至关重要.
- 在基底类乳腺癌中发现了关键基因 (如PRKCA,SOX6,FAM155A) 和丰富的CD8+ T细胞.
结论:
- 单细胞多原子分析是研究乳腺癌谱系发展的强大工具.
- 突出了关键的转录网络和基因,这些基因定义了基底和光线乳腺癌血统.
- 揭示了亚型特异性免疫细胞丰富,表明乳腺癌中的免疫功能障碍发生了变化.
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