A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization.
A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization.
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DOI：
10.1038/s41467-023-43999-1
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发表时间：
2023-12-12
影响因子：
16.6
通讯作者：
Aguirre, Aitor
中科院分区：
文献类型：
--
作者：
Volmert, Brett;Kiselev, Artem;Juhong, Aniwat;Wang, Fei;Riggs, Ashlin;Kostina, Aleksandra;O'Hern, Colin;Muniyandi, Priyadharshni;Wasserman, Aaron;Huang, Amanda;Lewis-Israeli, Yonatan;Panda, Vishal;Bhattacharya, Sudin;Lauver, Adam;Park, Sangbum;Qiu, Zhen;Zhou, Chao;Aguirre, Aitor
多能干细胞衍生的类器官可以概括体外器官发育的重要特征。我们假设，通过模仿子宫内妊娠的方面来创造人类心脏类器官（例如，添加代谢和激素因素）将导致更高的生理和解剖相关性。我们发现，使用这种自组织驱动的发育诱导策略产生的心脏类器官在转录和形态上与年龄匹配的人类胚胎心脏非常相似。我们还表明，他们概括了心脏发育的几个方面，包括大的心房和心室腔，心外膜器官的形成，和视黄酸介导的前后图案，模仿后心管阶段原始心脏中发现的发育过程。此外，我们通过探索昂丹司琼（一种给予孕妇并与先天性心脏病相关的药物）的作用，提供了该系统用于疾病建模的价值的概念验证。这些发现构成了合成心脏开发的重大技术进步，并为心脏疾病建模提供了强大的工具。多能干细胞衍生的类器官可以概括人类器官发育的重要标志，并正在成为人类研究的重要工具。在这里，作者报告了生成复杂的合成人类原始心脏类器官的重要技术步骤。
Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage primitive heart. Moreover, we provide proof-of-concept demonstration of the value of this system for disease modeling by exploring the effects of ondansetron, a drug administered to pregnant women and associated with congenital heart defects. These findings constitute a significant technical advance for synthetic heart development and provide a powerful tool for cardiac disease modeling. Pluripotent stem cell-derived organoids can recapitulate significant hallmarks of human organ development and are becoming critical tools for human research. Here, the authors report significant technical steps for generating sophisticated synthetic human primitive heart organoids.
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影响因子：
16.6
作者：
Funakoshi S;Fernandes I;Mastikhina O;Wilkinson D;Tran T;Dhahri W;Mazine A;Yang D;Burnett B;Lee J;Protze S;Bader GD;Nunes SS;Laflamme M;Keller G
通讯作者：
Keller G
影响因子：
5.9
作者：
Hikspoors JPJM;Kruepunga N;Mommen GMC;Köhler SE;Anderson RH;Lamers WH
通讯作者：
Lamers WH
影响因子：
14.8
作者：
Dekkers, Johanna F.;Alieva, Maria;Rios, Anne C.
通讯作者：
Rios, Anne C.
影响因子：
39.3
作者：
De Bruin, ML;Pettersson, M;Leufkens, HGM
通讯作者：
Leufkens, HGM
影响因子：
4.6
作者：
Hochgreb, T;Linhares, VL;Xavier-Neto, J
通讯作者：
Xavier-Neto, J