骨质细胞调节了血造干细胞利基的细胞
L M Calvi1, G B Adams, K W Weibrecht
1Endocrine Unit, Department of Medicine, Center for Human Genetics and Molecular Pediatric Disease, University of Rochester School of Medicine, Rochester, New York 14642, USA.
骨细胞通过Notch信号调节血液干细胞的数量. 副甲状腺激素 (PTH) 刺激骨质母细胞,增加造血干细胞 (HSC) 并改善移植存活率.
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
- 骨生物学 骨生物学 骨生物学
背景情况:
- 干细胞的命运受到微环境的影响,但它们在哺乳动物中仍然定义不佳.
- 血液形成,血细胞成分的形成,是局部在骨髓.
研究的目的:
- 为了调查骨源调节信息是否会影响造血干细胞 (HSC).
- 探索骨质母细胞在骨髓利基内调节HSCs中的作用.
主要方法:
- 评估了具有骨质母细胞特异性,激活PTH/PTHrP受体 (PPRs) 的转基因小鼠.
- 副甲状腺激素 (PTH) 用于激活PPRs在体外和体内.
- 评估了Notch激活,并使用马分泌酶抑制来阻止Notch信号传输.
主要成果:
- 通过PPR刺激的骨质母细胞数量增加,产生高水平的Jagged 1,并支持Notch1激活时HSC的增加.
- PTH治疗增加了 stromal 培养中的骨质母细胞,并增强了 ex vivo 原始造血细胞生长,这种细胞生长被马分泌酶抑制阻断.
- 在野生动物中,PTH注射增加了HSC,并在骨髓移植后显著改善了存活率.
结论:
- 骨质细胞是高质细胞的调节成分,通过Notch激活影响高质细胞功能.
- 准利基细胞或信号通路为基于干细胞的疗法提供了潜在的治疗策略.
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