日本京都大学Cantas Alev研究小组实现在体外重建人类体节发生。相关论文于2022年12月21日在线发表于国际学术期刊《自然》。
研究人员介绍了一种基于多能干细胞（PSC）的人类分节和体节发生的三维模型，被命名为“axioloid”，它准确地捕捉了分节时钟的振荡动态和体外连续体节形成的形态学和分子学特征。axioloid显示了形成体节的正确头尾形态和强大的前-后FGF/WNT信号梯度和视黄酸（RA）信号成分。研究人员发现RA信号在形成分节的稳定中起到了意想不到的关键作用，表明RA和细胞外基质（ECM）对体节的形成和上皮化有不同的、但也是协同作用。重要的是，比较分析表明axioloid与人类胚胎有惊人的相似性，axioloid中存在的HOX编码进一步验证了这一点。最后，研究人员通过使用具有HES7和MESP2突变的病人样iPSC，证明了axioloid在研究人类先天性脊柱疾病发病机制方面的效用。这些结果表明，axioloid代表了研究人类轴向发育和疾病的一个有前途的新平台。
据介绍，脊椎动物的分节身体结构是在体节发生过程中建立的，这在模式生物中是一个很好的研究过程，但由于伦理和技术上的限制，在人类中仍然很难找到。尽管最近以PSC为基础的方法取得了进展，但在空间和时间上有力地再现人类体节发生的模型在很大程度上仍然缺乏。
附：英文原文
Title: Reconstituting human somitogenesis in vitro
Author: Yamanaka, Yoshihiro, Hamidi, Sofiane, Yoshioka-Kobayashi, Kumiko, Munira, Sirajam, Sunadome, Kazunori, Zhang, Yi, Kurokawa, Yuzuru, Ericsson, Rolf, Mieda, Ai, Thompson, Jamie L., Kerwin, Janet, Lisgo, Steven, Yamamoto, Takuya, Moris, Naomi, Martinez-Arias, Alfonso, Tsujimura, Taro, Alev, Cantas
Issue&Volume: 2022-12-21
Abstract: The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms, but remains largely elusive in humans due to ethical and technical limitations. Despite recent advances with pluripotent stem cell (PSC)-based approaches1-5, models that robustly recapitulate human somitogenesis in both space and time are still largely missing. Here, we introduce a PSC-derived mesoderm-based 3D model of human segmentation and somitogenesis, which we termed ‘axioloid’, that captures accurately the oscillatory dynamics of the segmentation clock and the morphological and molecular characteristics of sequential somite formation in vitro. Axioloids show proper rostrocaudal patterning of forming segments and robust anterior-posterior FGF/WNT signaling gradients and retinoic acid (RA) signaling components. We identify an unexpected critical role of RA signaling in the stabilization of forming segments, indicating distinct, but also synergistic effects of RA and extracellular matrix (ECM) on the formation and epithelialization of somites. Importantly, comparative analysis demonstrates striking similarities of axioloids to the human embryo, further validated by the presence of a HOX code in axioloids. Lastly, we demonstrate the utility of axioloids to study the pathogenesis of human congenital spine diseases, by using patient-like iPSCs with mutations in HES7 and MESP2. These results suggest that axioloids represent a promising novel platform to study axial development and disease in humans.
DOI: 10.1038/s41586-022-05649-2
Source: https://www.nature.com/articles/s41586-022-05649-2
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
