SOX18强制表达将血源性内皮衍生的原始细胞从T转移到NK淋巴管道
Ho Sun Jung1, Kran Suknuntha2,3, Yun Hee Kim2
1Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA.
iScience
|May 30, 2023
概括
人类多能干细胞 (hPSC) 中的SOX18基因表达促进了自然杀手 (NK) 细胞的发展. 这一发现增强了对血液细胞形成的理解,并提供了一种用于免疫治疗的NK细胞生成的新方法.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 血源性内皮 (HE) 对于胚胎血细胞形成至关重要.
- 从人类多能干细胞 (hPSCs) 改善血液制造需要了解HE发育的分子调节者和血统承诺.
- SOX18是一种转录因子,在HE分化中具有潜在的作用.
研究的目的:
- 调查SOX18在HE规范和hPSCs血系发展中的作用.
- 为了确定SOX18是否可以增强特定的血细胞系,特别是用于治疗应用.
主要方法:
- 利用SOX18诱导的hPSC来控制基因表达.
- 分析了HE规范,动脉标记物,HOXA基因表达和淋巴细胞分化.
- 在SOX18诱导时,在内皮转化为血液形成转变 (EHT) 期间检查的血液形成原始体 (HP) 种群和血统承诺.
- 评估了与T细胞和Toll类受体信号传递相关的基因表达变化.
主要成果:
- 在中皮阶段强迫SOX18表达对动脉HE特异性和淋巴细胞分化的影响最小.
- 在EHT期间的SOX18诱导显著增加了NK细胞谱系的承诺,而不是T细胞的承诺.
- 这与多能HPs (CD34+CD43+CD235a/CD41a-CD45-) 的扩张和T细胞和Toll-like受体通路中的改变基因表达有关.
结论:
- 在EHT期间,SOX18在引导HE衍生的原始细胞向NK细胞系承诺方面发挥着关键作用.
- 这些发现促进了对淋巴细胞特异性的理解.
- SOX18为提高hPSCs的NK细胞生产提供了一种用于免疫治疗目的的新工具.
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