克洛赫是一种bHLH-PAS转录因子,驱动血液血管特异性
Sven Reischauer1,2, Oliver A Stone1,2, Alethia Villasenor1,2
1Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA.
Nature
|July 15, 2016
概括
克洛赫基因被确定为控制血液和血管细胞的主调节器. 这一发现增强了对胚胎早期发育和细胞生成的理解.
科学领域:
- 发育生物学
- 遗传学
- 细胞生物学
背景情况:
- 血管和造血细胞对于胚胎发育和器官功能至关重要.
- 斑马鱼中的克洛奇基因已知对这些细胞类型的发展至关重要,但由于其基因组位置,其分离是具有挑战性的.
- 克洛赫突变导致内皮细胞和造血细胞的丧失以及心肌细胞的增加.
研究的目的:
- 为了分离和描述克洛希基因.
- 了解其在内皮细胞和造血细胞的特异化中的作用.
- 研究其进化保存和细胞生成中的潜在应用.
主要方法:
- 使用Cloche的删除等位基因识别候选基因.
- 使用系统的基因组编辑来测试每个候选人.
- 在斑马鱼中进行功能增强和表观试验.
- 在斑马鱼突变体中测试了哺乳动物的形骨架功能.
主要成果:
- 成功隔离了克洛希基因,确定它是含有PAS域的bHLH转录因子.
- 在晚期胃化过程中表达特定的时空模式.
- 显示 cloche 诱导内皮基因表达和etv2 和tal1 的上游功能.
- 通过与哺乳动物 ортолог的救援实验证实了在脊椎动物血管生成和血液形成中的保留作用.
结论:
- 克洛赫是内皮细胞和造血细胞命运的主要调节者.
- 它的鉴定为早期中层层多样化提供了关键的见解.
- 这一发现可能有助于改进在体外和体内生成内皮细胞和造血细胞的方法.
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