小柯机器人

科学家建立模拟人肝胆胰腺发生的类器官模型
2019-09-26 13:55

美国辛辛那提儿童医院医疗中心Takanori Takebe团队的最新研究建立了模拟人类肝胆胰腺多器官发生的类器官模型。相关论文2019年9月25日在线发表在《自然》杂志上。

研究人员报道了人类多能干细胞的三维培养,发现了肝脏、胆汁和胰腺结构的连续模式化和动态形态发生。从人类多能干细胞分化而来的前肠球体和后肠球体之间的边界相互作用使得视黄酸依赖的肝胆胰脏器官结构域在前肠-中肠边界类动物体中存在,而不需要外在因素。移植物衍生的组织以中肠衍生物为主,长期培养的显微解剖的肝胆胰类器官发育成分离的多器官类似物,并概括了早期形态发生事件,包括三个不同且相互连接的器官结构的内陷和分支,使人联想起源自小鼠的前肠中肠培养物。如在体内观察到的,HES1基因突变引起的多器官结构域的错误分离消除了胆汁特异性培养的潜力。

总而言之,研究人员证明可以通过并列前肠和中肠组织建立实验性多器官整合模型,并可能作为研究复杂的人类内胚层器官发生的易处理、可操纵和易获取的模型。

据了解,器官发生是一个复杂且相互联系的过程,由多个边界组织相互作用而实现。但是,尚不清楚各个相邻的部分如何协调以建立一个完整的多器官结构。

附:英文原文

Title: Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary

Author: Hiroyuki Koike, Kentaro Iwasawa, Rie Ouchi, Mari Maezawa, Kirsten Giesbrecht, Norikazu Saiki, Autumn Ferguson, Masaki Kimura, Wendy L. Thompson, James M. Wells, Aaron M. Zorn, Takanori Takebe

Issue&Volume: 2019-09-25

Abstract: 

Organogenesis is a complex and interconnected process that is orchestrated by multiple boundary tissue interactions1,2,3,4,5,6,7. However, it remains unclear how individual, neighbouring components coordinate to establish an integral multi-organ structure. Here we report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut–midgut boundary organoids in the absence of extrinsic factors. Whereas transplant-derived tissues are dominated by midgut derivatives, long-term-cultured microdissected hepato-biliary-pancreatic organoids develop into segregated multi-organ anlages, which then recapitulate early morphogenetic events including the invagination and branching of three different and interconnected organ structures, reminiscent of tissues derived from mouse explanted foregut–midgut culture. Mis-segregation of multi-organ domains caused by a genetic mutation in HES1 abolishes the biliary specification potential in culture, as seen in vivo8,9. In sum, we demonstrate that the experimental multi-organ integrated model can be established by the juxtapositioning of foregut and midgut tissues, and potentially serves as a tractable, manipulatable and easily accessible model for the study of complex human endoderm organogenesis.

DOI: 10.1038/s41586-019-1598-0

Source:https://www.nature.com/articles/s41586-019-1598-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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