脂肪症驱动单细胞衍生的巨细胞积累在人类的代谢功能障碍相关的脂肪肝疾病
Mandy M Chan1,2,3, Sabine Daemen4, Joseph W Beals5
1Diabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA.
JHEP reports : innovation in hepatology
|October 23, 2023
概括
与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 涉及肝脏巨细胞. 单细胞衍生的巨细胞 (MdMs) 积累脂质,并被早期招募,这表明在MAFLD进展中发挥了作用.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 代谢疾病 代谢疾病
背景情况:
- 代谢功能障碍相关的脂肪肝疾病 (MAFLD) 是一种普遍存在的肥胖并发症,其特征是肝硬化症.
- 虽然动物模型显示脂肪肝中巨细胞的变化,但人类关于肝脏巨细胞异质性和肥胖症的数据有限.
研究的目的:
- 在早期MAFLD期间研究人类肝脏的巨细胞异质性.
- 建立人类MAFLD和临床前模型之间的翻译联系.
主要方法:
- 使用流细胞计,免疫光和显微镜分析了21名减肥手术患者的肝脏组织.
- 在样本子集 (n=3) 上进行单细胞RNA测序.
- 通过MRI和组织学评估肝脏内甘油三含量;在小鼠模型中进行验证.
主要成果:
- 在人类脂肪肝中确定了四个巨细胞群,包括库普弗细胞和单细胞衍生巨细胞 (MdMs).
- 巨细胞基因表达反映了小鼠MAFLD模型中的基因表达.
- 肝脏CD14+单细胞/巨细胞计数与肥胖症程度相关;MdM显示脂质积累增加,并在小鼠模型中早期被招募.
结论:
- 人类MAFLD肝脏含有巨细胞子集,与小鼠模型一致.
- 招募的髓状细胞与人类肝脏肥胖症相关.
- 在MAFLD早期阶段,MdMs在脂质吸收中发挥作用.
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