人类多能干细胞的有针对性的分化成肠道组织 in vitro
Jason R Spence1, Christopher N Mayhew, Scott A Rankin
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA.
Nature
|December 15, 2010
概括
研究人员开发了一种新方法,可以从多能干细胞 (PSC) 培育出三维人类肠道器官. 这一突破使肠道发育和肠道内分泌异位症等疾病的详细研究成为可能.
科学领域:
- 发育生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 之前的研究成功地将多能干细胞 (PSC) 在体外分化为特定器官细胞类型,如肝肝细胞和胰腺内分泌细胞.
- 在体外生成复杂的三维 (3D) 器官组织仍然是翻译研究的重大障碍.
研究的目的:
- 建立一个强大而有效的过程,以在体外将人类PSC分化为肠道组织.
- 用时间生长因子操纵来模仿胚胎肠道发育.
- 为研究人类肠道发育和疾病创建模型.
主要方法:
- 时间操纵生长因子 (活性素,FGF,Wnt) 以引导PSC分化.
- 模仿胚胎发育阶段:最终的内皮形成,后部内皮造型,后肠特异化和形态发生.
- 使用亲肠道培养系统来促进生长,形态发生和细胞分化.
主要成果:
- 产生的3D肠道有机体,具有极化,柱状表皮组织成状和密室状结构.
- 有机体中含有功能性肠细胞,杯细胞,帕内斯细胞和肠内分泌细胞.
- 确定WNT3A和FGF4对后肠特异性至关重要,FGF4对形态发生至关重要;NEUROG3对肠内分泌细胞发育至关重要.
结论:
- 人类肠道干细胞在发育过程中是de novo形成的.
- NEUROG3对于人体肠内分泌细胞在体外的发育是必要的,也是足够的.
- 来自PSC的人类肠道组织为研究肠道发育和疾病提供了新的途径.
相关概念视频
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