内皮细胞和周血管细胞维持了血液形成干细胞
Lei Ding1, Thomas L Saunders, Grigori Enikolopov
1Howard Hughes Medical Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|January 28, 2012
概括
干细胞因子 (SCF) 对于维持造血干细胞 (HSC) 至关重要. 研究表明,SCF主要由骨髓中的周血管细胞产生,其中内皮细胞和Lepr+细胞是关键来源.
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
- 骨髓研究的利基研究
背景情况:
- 造血干细胞 (HSC) 依赖于特定的利基环境进行维护.
- 关键的HSC维护因子的细胞来源,如干细胞因子 (SCF),仍然在很大程度上未确定.
- 骨髓内SCF (KITL) 是骨髓内HSC维护的关键因素.
研究的目的:
- 系统地研究骨髓内的SCF细胞表达模式.
- 确定负责生产SCF的特定细胞类型,这对于HSC维护至关重要.
- 阐明来自不同细胞源的SCF在HSC频率和功能中的作用.
主要方法:
- 使用Scf ((gfp) 敲进小鼠来跟踪SCF表达模式.
- 在各种骨髓细胞群体中执行SCF的条件删除,包括造血细胞,骨质母细胞,内皮细胞和表达Lepr的周围血管层细胞.
- 使用遗传模型评估SCF条件删除后的HSC频率和功能.
主要成果:
- 主要观察到SCF表达在骨髓周围的血管细胞中.
- 从造血细胞,骨质母细胞或巢素表达细胞中条件删除SCF并没有影响HSC.
- 在SCF从内皮细胞或Lepr表达的周脉层细胞中删除后,发生了HSC的枯竭.
- 当SCF从内皮细胞和表达Lepr的周血管细胞中被删除时,观察到显著的HSC损失.
结论:
- HSCs位于骨髓中的周围血管中.
- 周血管内的多种细胞类型通过SCF生产促进HSC维护.
- 内皮细胞和表达Lepr的周脉层细胞是SCF维护HSC的关键细胞来源.
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