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二次胆汁酸通过骨髓原体的维生素D受体起作用,促进骨髓构造
Brandon Thompson1, Shan Lu2, Julio Revilla1
1Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA.
Blood advances
|June 5, 2023
概括
二次胆酸,脱氧胆酸 (DCA) 和石胆酸 (LCA),通过通过维生素D受体 (VDR) 扩大粒细胞-单细胞原生体 (GMP) 来增强骨髓骨质形成. 这揭示了微生物组代谢物和血液形成之间的直接联系.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 微生物代谢产物可以影响血细胞的形成 (血液形成).
- 胆汁酸在血液形成中的特定作用和机制尚不清楚.
- 二次胆酸,如脱氧胆酸 (DCA) 和石胆酸 (LCA),是肠道微生物的产物.
研究的目的:
- 为了研究二次胆汁酸对骨髓骨髓形成的影响.
- 确定细胞点和分子机制,即胆汁酸影响造血干细胞和原始细胞 (HSPCs).
- 阐明维生素D受体 (VDR) 在胆酸介导的血液形成中的作用.
主要方法:
- 用DCA和LCA处理骨髓细胞和分类的HSPC.
- 使用殖民地形成单元-粒细胞和巨细胞 (CFU-GM) 试验评估原始细胞扩张.
- 使用VDR缺陷模型对VDR依赖性的分析.
- 在DCA治疗后,对粒细胞-单细胞原体 (GMP) 的单细胞RNA测序.
主要成果:
- DCA和LCA治疗增加了骨髓骨髓形成.
- DCA和LCA优先扩大了CFU-GM和GMP种群.
- HSPCs对DCA的直接暴露足以增加GMPs.
- VDR对于DCA诱导的CFU-GM和GMP扩张至关重要.
- 在GMP中,DCA上调调节了髓状细胞分化和增殖基因.
结论:
- 二次胆酸,特别是DCA,通过扩大GMP直接促进骨髓形成.
- 这种扩张依赖于维生素D受体 (VDR).
- 涉及胆汁酸的微生物群与宿主相互作用可以直接影响骨髓血液形成,并可能影响炎症和传染病.
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