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具有增强TWIST1表达的克隆MDS/AML细胞重新编程骨髓MSCs的分化

Hongjiao Li¹, Yi Wang², Fenfang Yang¹

¹Key Laboratory of Resource Biology and Biotechnology of Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, China.

|September 25, 2023

概括

骨髓发育综合征 (MDS) 和急性髓性白血病 (AML) 细胞促进脂肪细胞分化,并抑制骨髓中介质干细胞 (BMMSCs) 的骨细胞形成,促进癌症生长. 准TWIST1可能为这些血液癌症提供新的治疗方法.

科学领域:

血液学血液学血液学
干细胞生物学干细胞生物学
癌症生物学癌症生物学

背景情况:

骨髓发育综合征 (MDS) 和急性髓性白血病 (AML) 中的介质干细胞 (MSC) 呈现出改变的分化,影响骨髓微环境.
通过MDS/AML克隆细胞影响MSC分化的精确机制仍然不完全理解.

研究的目的:

为了研究MDS/AML克隆细胞和骨髓衍生中酶干细胞 (BMMSCs) 差异化之间的相互作用.
在MDS/AML的背景下识别BMMSC分化变化的分子驱动因素.

主要方法:

利用临床样本,共同培养模型和小鼠模型来研究MDS/AML和BMMSC相互作用.
采用质谱和细胞因子阵列来识别关键分子介质.
研究了转录因子TWIST1的作用及其下游效应.

主要成果:

发现MDS/AML克隆细胞促进了基分化,并抑制了BMMSCs的骨质分化.
观察到这种改变的BMMSC差异化促进了MDS扩张.
在MDS/AML细胞中高表达的TWIST1驱动IFN-γ分泌量的增加,导致STAT1依赖的氧化应激和歪曲的BMMSC分化.

结论:

通过改变BMMSC分化,MDS/AML克隆细胞积极重塑骨髓微环境.
在恶性细胞中准像TWIST1这样的瘤基因是一种潜在的治疗策略,可以在MDS/AML和其他血液形成性恶性瘤中使骨髓利基正常化.

关键词:

在BMMSCs中,美国MDS/AML 骨质性/质性差异化分化这就是ROSOS ROS.这就是TWIST1的特点.

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