在器官生成过程中组织寄存的巨细胞的规范
Elvira Mass1, Ivan Ballesteros1, Matthias Farlik2
1Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Science (New York, N.Y.)
|August 6, 2016
概括
胚胎发育涉及早期殖民器官的前细胞. 然后组织特异性因素将这些细胞多样化为专门的巨细胞,这对于器官生成和稳态至关重要.
科学领域:
- 发育生物学
- 免疫学
- 细胞生物学
背景情况:
- 组织寄存的巨细胞对于胚胎发育,组织平衡和修复至关重要.
- 控制巨分化的精确机制尚不完全理解.
研究的目的:
- 阐明控制胚胎发育过程中的组织寄生性巨细胞分化机制.
- 确定涉及巨特征的关键细胞前体和分子事件.
主要方法:
- 利用小鼠模型追踪红骨髓原体及其分化为前细胞 (pMacs).
- 研究了pMacs对胚胎的化学因子受体依赖殖民.
- 分析了转录调节剂在早期巨细胞的组织特异多样化中的作用.
- 研究了 Id3 失活对肝脏巨细胞发育和库普费尔细胞群的影响.
主要成果:
- 从胚胎第9.5天开始,红细胞前代产生前细胞 (pMacs),以化学因子受体依赖的方式殖民整个胚胎.
- 在pMac中核心巨程序通过早期巨中转录调节者的组织特异性表达迅速多样化.
- 在成年小鼠中,Id3的失活会扰乱肝细胞的发育,导致选择性的库普费尔细胞缺乏.
- 通过pMacs对器官原体的殖民化先于它们的特异化成为独特的组织巨细胞.
结论:
- 巨的分化与机体发生有内在的联系,pMacs的早期殖民,其次是组织特定的规范.
- 这一过程对于产后组织中观察到的多样化的巨细胞群产生至关重要.
- Id3 在肝脏巨细胞 (包括库普弗细胞) 的规范和维护中起着至关重要的作用.
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