心脏和内胚层联盟:多向性器官样体用于共同发展建模。
Alliance of Heart and Endoderm: Multilineage Organoids to Model Co-development.
发表日期:2023 Feb 17
作者:
Wai Hoe Ng, Barbie Varghese, Hongpeng Jia, Xi Ren
来源:
CIRCULATION RESEARCH
摘要:
动物模型研究描绘了中胚层来源心脏发生的重要性,强调来自相邻内胚层组织的信号在协调心脏形态发生中的作用。虽然心脏器官样本等体外模型已经显示了重复人类心脏生理的巨大潜力,但是它们无法捕捉共同发育的心脏和内胚层器官之间所发生的复杂信息交流,部分原因是它们有明显的种属源头区别。为了解决这一长期以来的挑战,最近有关同时含心脏和内胚层衍生物的多线age器官样本的报告已经推动了解析器官间交互信息如何影响其不同形态发生的努力。这种共同分化系统已经产生了有趣的结果,证实了诱导心脏特化与原始前肠、肺部或肠道谱系所需的共同信号需求。总的来说,这些多线age心脏器官样本提供了一个前所未有的窗口进入人类发育,揭示了内胚层和心脏如何合作指导形态发生、分型和成熟。此外,经过时空重组,共同出现的多线age细胞自组成不同的区域,如在心脏-前肠、心脏-肠和心肺器官样本中,并进行细胞迁移和组织重组,以建立组织边界。展望未来,这些包含心脏的多线age器官样本将启发未来改善细胞来源的再生干预策略,并为疾病调查和药物测试提供更有效的模型。在本综述中,我们将介绍协同心脏和内胚层形态发生的发育背景,讨论在体内诱导心脏和内胚层衍生物的策略,并最终评论由此突破所启示的挑战和令人兴奋的新研究方向。
Studies in animal models tracing organogenesis of the mesoderm-derived heart have emphasized the importance of signals coming from adjacent endodermal tissues in coordinating proper cardiac morphogenesis. Although in vitro models such as cardiac organoids have shown great potential to recapitulate the physiology of the human heart, they are unable to capture the complex crosstalk that takes place between the co-developing heart and endodermal organs, partly due to their distinct germ layer origins. In an effort to address this long-sought challenge, recent reports of multilineage organoids comprising both cardiac and endodermal derivatives have energized the efforts to understand how inter-organ, cross-lineage communications influence their respective morphogenesis. These co-differentiation systems have produced intriguing findings of shared signaling requirements for inducing cardiac specification together with primitive foregut, pulmonary, or intestinal lineages. Overall, these multilineage cardiac organoids offer an unprecedented window into human development that can reveal how the endoderm and heart cooperate to direct morphogenesis, patterning, and maturation. Further, through spatiotemporal reorganization, the co-emerged multilineage cells self-assemble into distinct compartments as seen in the cardiac-foregut, cardiac-intestine, and cardiopulmonary organoids and undergo cell migration and tissue reorganization to establish tissue boundaries. Looking into the future, these cardiac incorporated, multilineage organoids will inspire future strategies for improved cell sourcing for regenerative interventions and provide more effective models for disease investigation and drug testing. In this review, we will introduce the developmental context of coordinated heart and endoderm morphogenesis, discuss strategies for in vitro co-induction of cardiac and endodermal derivatives, and finally comment on the challenges and exciting new research directions enabled by this breakthrough.