一个单细胞造血微环境图谱揭示了骨髓血管的逐渐成熟
Lan-Yue Ma1,2,3,4, Zhao-Hua Deng1,2,3,4, Ke Bai5
1Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Cell regeneration (London, England)
|December 3, 2025
概括
这项研究绘制了血液造血干细胞和原生细胞 (HSPC) 与其血管利基之间的相互作用,跨越了发育和物种. 它确定中作为一个关键因素,增强了造血重构.
科学领域:
- 血液学 血液学 血液学
- 发展生物学 发展生物学
- 血管生物学 血管生物学
背景情况:
- 血造干细胞和原生细胞 (HSPC) 与血管利基的相互作用对于血液系统的恒温至关重要.
- 目前还没有一个全面的地图,描述了这种跨发育阶段和物种的相互作用.
研究的目的:
- 创建一个跨物种的,多阶段的ATLAS的HSPC-血管利基相互作用.
- 在终身HSPC发展过程中识别血管利基的动态变化.
- 发现影响HSPC行为的新兴利基因素.
主要方法:
- 综合单细胞转录基因数据来自人类和小鼠的HSPC和血管.
- 分析了六个发育时间点,两个器官 (胎儿肝脏,骨髓) 和两个物种的数据.
- 进行基因表达,通路和细胞间通信的比较分析.
- 通过使用中敲击小鼠和抑制剂进行功能验证.
主要成果:
- 揭示了人类胎儿和成人骨髓之间基因表达和细胞通信的显著差异,在小鼠中大致保留.
- 记录了小鼠骨髓血管的逐步成熟,包括SCF和CXCL12表达.
- 在骨髓内皮细胞中确定了特定器官的利基特征和与年龄相关的转录性变化.
- 发现midkine作为一种新的利基因素,当其活性受到抑制时,可以增强造血复合.
结论:
- 介绍了跨物种和发育阶段的HSPC-血管利基相互作用的全面地图.
- 突出了血管的动态性质及其在终身造血中的作用.
- 确定中作为一种潜在的治疗点,用于增强造血复合.
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