表观遗传可塑性与细胞相互作用合作,以指导胰腺瘤发生
Cassandra Burdziak1,2, Direna Alonso-Curbelo3,4, Thomas Walle1,5,6,7
1Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
概括
早期胰腺癌的表观遗传可塑性允许细胞采用多种状态,影响瘤的进展. 了解这种细胞可塑性和组织交叉对话可能会导致新的拦截策略.
科学领域:
- 癌症生物学
- 表观遗传学
- 免疫学
背景情况:
- 细胞对引发瘤的反应是异质的,这表明早期瘤中表观遗传的作用没有特征.
- 表观遗传可塑性可能会从最初相似的细胞驱动不同的瘤命运.
研究的目的:
- 研究表观遗传可塑性在早期胰腺癌的起源和影响.
- 确定导致胰腺瘤的细胞状态和组织层面的相互作用.
主要方法:
- 对正常,炎症,前恶性和恶性胰腺组织进行单细胞分析.
- 在细胞间通信位点进行染色体重塑分析.
- 推断方法来识别信号基因模块和组织交叉对话.
主要成果:
- 识别了针对不同瘤命运的异质细胞状态.
- 将细胞状态异质性与通信位点的染色体重塑联系起来.
- 揭示了皮质细胞和免疫细胞之间的瘤驱动反循环, 在小鼠中得到验证.
结论:
- 在胰腺癌中发现了特定瘤组织重塑程序.
- 在早期的瘤进展中,表观遗传可塑性和细胞间的沟通至关重要.
- 这项计划提供了潜在的瘤拦截目标.
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