全基因组CRISPR屏幕识别了Menin和SUZ12作为人类发育时间的调节者
Nan Xu1,2, Hyein S Cho1, James O S Hackland1
1The Center for Stem Cell Biology and Developmental Biology program; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature cell biology
|September 2, 2025
概括
人类胚胎发育时间由表观遗传因素Menin和SUZ12控制. 这些因素的丧失通过改变色素标记来加速细胞命运的获取,从而加快基因在分化过程中的激活.
科学领域:
- 发育生物学
- 表观遗传学
- 干细胞生物学
背景情况:
- 胚胎发育时间因物种而异,人类的发育速度特别缓慢.
- 这种特定物种的发育速度反映在干细胞模型中,这表明细胞内有固有时钟.
- 了解调节发育速度的分子机制对于再生医学和发育研究至关重要.
研究的目的:
- 确定控制人类胚胎发育速度的表观遗传调节剂.
- 研究Menin和SUZ12在调节神经分化时间中的作用.
- 探索这些因素对染色质状态和基因激活的影响.
主要方法:
- 在经历神经外皮分化的人类胚胎干细胞中进行全基因组CRISPR-Cas9淘汰查.
- 对Menin和SUZ的遗传和药理功能丧失研究12.
- 在双价促进体中分析基因组修饰 (H3K4me3和H3K27me3).
主要成果:
- 在神经分化过程中,男性素和SUZ12被确定为调节PAX6表达速度的关键表观遗传因素.
- 通过改变H3K4me3和H3K27me3在双价促进体中的平衡,Menin或SUZ12的损失加速了细胞命运的获得.
- 在控制分化速度方面观察到Menin和SUZ12之间的协同作用.
- 在终极内皮,心肌细胞和神经元分化模型中也观察到加速分化.
结论:
- 人体干细胞发育时间的关键表观遗传调节剂是menin和SUZ12.
- 染色体双价是驱动不同胚胎层和阶段的发育时间的一般机制.
- 针对Menin和SUZ12为治疗应用提供了调节差异化速度的潜在策略.
相关概念视频
01:59CRISPR
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
02:53CRISPR and crRNAs
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
01:59CRISPR
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...