造血基的细胞-细胞相互作用及其在急性髓性白血病中的变化
Sarah Ennis1,2, Alessandra Conforte3, Eimear O'Reilly3
1The SFI Centre for Research Training in Genomics Data Science, Galway, Ireland.
iScience
|June 19, 2023
概括
研究人员在健康和急性髓性白血病 (AML) 中描述了骨髓 (BM) 微环境. AML破坏了BM小区,通过改变细胞相互作用和信号传递促进白血病细胞生长.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 细胞微环境 细胞微环境
背景情况:
- 骨髓 (BM) 微环境对于日常的血细胞生产至关重要.
- 尽管它在造血和急性髓性白血病 (AML) 等疾病中的重要性很大,但BM领域的了解仍然很少.
研究的目的:
- 在健康状态和AML中提供BM利基的高分辨率表征.
- 在AML进展过程中识别BM利基内的细胞组成和基因表达的变化.
主要方法:
- 建立了一个包括339,381个BM细胞的单细胞基因表达数据库.
- 分析了健康与AML的细胞类型比例和基因表达模式.
- 预测血造干细胞和原生细胞 (HSPC) 和其他BM细胞之间的细胞间相互作用.
主要成果:
- 在AML中观察到BM细胞类型比例和基因表达的显著变化,表明受损的利基.
- AML表明,预测的相互作用扩大,促进HSPC细胞粘附,免疫抑制和细胞因子信号传递.
- 转化生长因子β1 (TGFB1) 信号被确定为AML的广泛相互作用,驱动白血病细胞静止.
结论:
- 在AML中,BM利基被显著重塑,促进白血病的生长.
- 改变的细胞相互作用和信号通路,特别是TGFB1,有助于增强AML-HSPC的竞争力和有利于白血病的微环境.
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