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人类心脏类器官可重现早期心脏和前肠的发育
作者:小柯机器人 发布时间:2021/2/10 15:27:04

德国汉诺威医学院Robert Zweigerdt、Lika Drakhlis等研究人员合作发现,人类心脏类器官可重现早期心脏和前肠的发育。该研究于2021年2月8日在线发表于国际一流学术期刊《自然—生物技术》。

通过将人类多能干细胞聚集体埋入基质胶中,然后通过小分子的双相WNT途径调控定向心脏分化,研究人员获得了复杂的、高度结构化的三维心脏形成类器官(HFO)。HFO由一层内膜样细胞内衬并被中隔横隔样结构包围的心肌层组成。它们还包含在空间和分子上截然不同的前肠内胚层组织以及血管网络。HFO的结构与心管形成之前的早期天然心脏结构非常相似。

通过揭示NKX2.5基因敲除的HFO表型与转基因小鼠中心脏畸形表型的相似性,研究人员证明HFO可被应用于体外遗传缺陷的研究。 

据介绍,肠、脑、肾和其他器官已经建立了早期组织发育的类器官模型,但是缺乏心脏的类似方法。

附:英文原文

Title: Human heart-forming organoids recapitulate early heart and foregut development

Author: Lika Drakhlis, Santoshi Biswanath, Clara-Milena Farr, Victoria Lupanow, Jana Teske, Katharina Ritzenhoff, Annika Franke, Felix Manstein, Emiliano Bolesani, Henning Kempf, Simone Liebscher, Katja Schenke-Layland, Jan Hegermann, Lena Nolte, Heiko Meyer, Jeanne de la Roche, Stefan Thiemann, Christian Wahl-Schott, Ulrich Martin, Robert Zweigerdt

Issue&Volume: 2021-02-08

Abstract: Organoid models of early tissue development have been produced for the intestine, brain, kidney and other organs, but similar approaches for the heart have been lacking. Here we generate complex, highly structured, three-dimensional heart-forming organoids (HFOs) by embedding human pluripotent stem cell aggregates in Matrigel followed by directed cardiac differentiation via biphasic WNT pathway modulation with small molecules. HFOs are composed of a myocardial layer lined by endocardial-like cells and surrounded by septum-transversum-like anlagen; they further contain spatially and molecularly distinct anterior versus posterior foregut endoderm tissues and a vascular network. The architecture of HFOs closely resembles aspects of early native heart anlagen before heart tube formation, which is known to require an interplay with foregut endoderm development. We apply HFOs to study genetic defects in vitro by demonstrating that NKX2.5-knockout HFOs show a phenotype reminiscent of cardiac malformations previously observed in transgenic mice. Heart-forming organoids model early cardiac development.

DOI: 10.1038/s41587-021-00815-9

Source: https://www.nature.com/articles/s41587-021-00815-9

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex