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通过实时单细胞分化映射识别肠内分泌调节剂
Helmuth Gehart1, Johan H van Es2, Karien Hamer1
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre (UMC) Utrecht, 3584 CT Utrecht, the Netherlands.
Cell
|February 5, 2019
概括
了解肠内分泌细胞的分化是关键. 这项研究实时绘制细胞发育图,识别新调节剂,并揭示细胞类型随时间变化.
科学领域:
- 细胞生物学
- 发育生物学
- 胃肠病学
背景情况:
- 肠道内分泌系结构的稳态调节还不太清楚.
- 肠内分泌细胞对于肠-大脑通信和代谢调节至关重要.
研究的目的:
- 在单细胞水平上实时解决肠内分泌过程中的转录变化.
- 创建肠内分泌层次结构及其子系的最终地图.
主要方法:
- 使用一种新型的Neurog3Chrono敲定基因和双光记者进行时间解析的单细胞转录组学.
- 在小鼠中使用条件淘汰和在肠道器官中使用CRISPR修饰进行验证.
主要成果:
- 产生了对肠内分泌层次和细分系的明确描述,具有差异化运动.
- 在L细胞中发现时间依赖的荷尔蒙可塑性.
- 确定并验证了六种影响肠内分泌表型的新候选调节剂 (Sox4,Rfx6,Tox3,Myt1,Runx1t1,Zcchc12).
结论:
- 时间解析的单细胞转录地图为研究肠内分泌差异化提供了全面的资源.
- 这项研究阐明了控制肠内分泌细胞发育的关键分子调节剂和动态.
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