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Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids
Cell Stem Cell ( IF 23.9 ) Pub Date : 2021-12-02 , DOI: 10.1016/j.stem.2021.11.007
Ana C Silva 1 , Oriane B Matthys 2 , David A Joy 2 , Mara A Kauss 3 , Vaishaali Natarajan 1 , Michael H Lai 1 , Diwaker Turaga 1 , Andrew P Blair 1 , Michael Alexanian 1 , Benoit G Bruneau 4 , Todd C McDevitt 5
Affiliation  

During embryogenesis, paracrine signaling between tissues in close proximity contributes to the determination of their respective cell fate(s) and development into functional organs. Organoids are in vitro models that mimic organ formation and cellular heterogeneity, but lack the paracrine input of surrounding tissues. Here, we describe a human multilineage iPSC-derived organoid that recapitulates cooperative cardiac and gut development and maturation, with extensive cellular and structural complexity in both tissues. We demonstrate that the presence of endoderm tissue (gut/intestine) in the organoids contributed to the development of cardiac tissue features characteristic of stages after heart tube formation, including cardiomyocyte expansion, compartmentalization, enrichment of atrial/nodal cells, myocardial compaction, and fetal-like functional maturation. Overall, this study demonstrates the ability to generate and mature cooperative tissues originating from different germ lineages within a single organoid model, an advance that will further the examination of multi-tissue interactions during development, physiological maturation, and disease.



中文翻译:

心脏和肠道组织的共同出现促进人 iPSC 衍生的类器官内的心肌细胞成熟

在胚胎发生过程中,靠近的组织之间的旁分泌信号有助于确定它们各自的细胞命运并发育成功能器官。类器官在体外模拟器官形成和细胞异质性的模型,但缺乏周围组织的旁分泌输入。在这里,我们描述了一种人类多向 iPSC 衍生的类器官,它概括了心脏和肠道的协同发育和成熟,在两种组织中都具有广泛的细胞和结构复杂性。我们证明,类器官中内胚层组织(肠道/肠)的存在有助于心脏组织特征的发育,这些特征是心管形成后阶段的特征,包括心肌细胞扩张、区室化、心房/结节细胞富集、心肌压实和胎儿- 功能成熟。总体而言,这项研究证明了在单个类器官模型中生成和成熟源自不同种系的合作组织的能力,

更新日期:2021-12-02
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