动态WNT信号控制着血造原生细胞与人类多能干细胞的分化
Mo Li1,2,3, Keiichiro Suzuki4,5, Mengge Wang6,7
1Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia. mo.li@kaust.edu.sa.
Science China. Life sciences
|March 13, 2025
概括
在从多能干细胞 (hPSC) 发育的人类造血干细胞/原始细胞 (HSPC) 发育过程中调节WNT信号是至关重要的. 晚期WNT抑制改善HSPC质量,提供更好的细胞疗法和疾病模型.
科学领域:
- 干细胞生物学 干细胞生物学
- 血液形成 血液形成 血液形成
- 分子信号传递是分子信号传递.
背景情况:
- 人类多能干细胞 (hPSCs) 具有产生研究和治疗的多样化造血系的潜力.
- 目前存在的局限性是由于对人类造血干细胞/原始细胞 (HSPC) 规范要求的不完全理解.
- 在hPSC衍生HPC (hPSC-HPC) 中异常WNT信号导致缺陷,例如自我更新和差异化受损.
研究的目的:
- 调查WNT信号在人类HSPC规范中的作用.
- 确定hPSC-HPC中差异化缺陷背后的分子机制.
- 为治疗应用开发改善hPSC-HPC质量的策略.
主要方法:
- 对hPSC-HPCs的转录组分析以确定信号通路失调.
- 转录因子可访问的染色体的全基因组映射.
- 小分子调制WNT信号通路.
主要成果:
- 在hPSC-HPC中异常的WNT信号导致线粒体功能障碍,HOX基因错误调节和自我更新受损.
- 激活WNT目标基因CDX2有助于分化缺陷.
- 晚期WNT抑制显著提高hPSC-HPC产量,自我更新,差异化潜力和分子形状.
- 骨髓体转录因子结合动机的过度代表表明骨髓体偏差的潜力.
结论:
- 动态WNT信号调节对于正确的人类HSPC规范至关重要.
- 用小分子调节WNT信号,使hPSC-HPCs正常化,使它们与内源性HSCs更相似.
- 这种方法为改善hPSC衍生的造血干细胞和祖先细胞的临床应用提供了一个有希望的策略.
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