M-CSF在单个造血干细胞中指导髓状细胞系命运
Noushine Mossadegh-Keller1, Sandrine Sarrazin, Prashanth K Kandalla
1Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.
Nature
|April 12, 2013
概括
压力诱导的细胞因子,如巨菌群刺激因子 (M-CSF),可以直接指示造血干细胞 (HSC) 采用髓状细胞命运,挑战以前对干细胞反应的理解.
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
- 免疫学 免疫学 免疫学
背景情况:
- 造血干细胞 (HSC) 在感染或炎症等压力期间产生新的血细胞.
- 细胞因子通常支持成熟细胞的产生,但细胞因子对HSCs的直接血统特征有争议.
- HSC承诺的启动通常归因于内在因素,而不是直接的细胞因子指令.
研究的目的:
- 调查骨髓细胞因子是否直接影响造血干细胞 (HSC) 血统承诺.
- 确定巨细胞殖民地刺激因子 (M-CSF) 是否可以直接诱导HSC中的骨髓分化.
主要方法:
- 在试验室中,用M-CSF刺激了纯化的小鼠HSCs.
- 用单细胞基因表达和视频成像来分析HSC反应.
- 在体内研究评估了M-CSF在系统性高水平下对HSC的影响.
主要成果:
- 在HSC中,M-CSF直接诱导骨髓质主调节器PU.1,独立于增殖.
- 在体外,M-CSF激活了PU.1促进体,并增加了髓状细胞受影响的细胞.
- 在体内,M-CSF刺激了PU.1的激活,并促进了HSC中的骨髓分化偏好.
结论:
- 血统特异性细胞因子,如M-CSF,可以直接指示HSCs在体外和体内改变细胞身份.
- 这一发现挑战了HSC应对环境挑战的传统观点.
- 压力诱导的细胞因子被认为是HSC命运决定的直接调节者.
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