细胞特异性基因表达可塑性对低氧的反应促进了高海拔适应性进化
Wen-Tian Wei1, Ze Yan1, Hui Wu1
1Frontiers Science Center for Molecular Design Breeding (MOE); State Key Laboratory of Animal Biotech Breeding; College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Science China. Life sciences
|March 7, 2026
概括
基因适应逆转细胞特异性基因表达可塑性,免疫细胞驱动适应. 这项研究揭示了缺氧适应机制和疾病洞察力.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 现型可塑性和遗传适应之间的相互作用是一个关键的进化问题.
- 关联可塑性和适应性的分子机制,特别是在环境变化 (如缺氧) 期间,仍未得到充分探索.
- 绵羊被用作模型生物来研究细胞对缺氧的反应.
研究的目的:
- 探索细胞特异性基因表达可塑性及其通过遗传适应的逆转.
- 为了确定分子网络和细胞变化涉及低氧适应.
- 研究细胞可塑性在低氧相关疾病中的作用.
主要方法:
- 对绵羊进行了平原到高原动物转移实验.
- 从大脑,心脏和肺组织中生成了27个scRNA-seq和54个snRNA-seq数据集.
- 分析了超过236,000个细胞和90万个细胞核中的基因表达.
主要成果:
- 揭示了细胞特异性基因表达可塑性,这种可塑性在很大程度上被遗传适应逆转.
- 确定免疫细胞具有高的逆向可塑性,通过选择促进适应.
- 发现了一个共同的调节网络 (AP-1→HIF-BHLHE41),在低氧反应中是细胞可塑性的基础.
- 观察到细胞可塑性,包括微质激活和内皮细胞到介质细胞的过渡,跨器官.
结论:
- 细胞表达可塑性是低氧适应的一个关键特征,由特定的调节网络驱动.
- 免疫细胞的可塑性在促进基因适应环境压力因素方面发挥着至关重要的作用.
- 了解细胞对缺氧的反应,可以了解相关疾病的发生率和进展.
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