小柯机器人

科学家实现人类体节发生的体外重建和解构
2022-12-23 10:36

美国布莱根妇女医院Olivier Pourquié课题组实现人类体节发生的体外重建和解构。相关论文于2022年12月21日在线发表在《自然》杂志上。

研究人员报道了人类多能干细胞(PSC)的新型三维培养系统,称为Somitoid和Segmentoid,它再现了具有前-后(AP)轴特征的体节样结构的形成。研究人员确定了分节时钟在将时间节律性转换为前后体节区间的空间规律性方面的关键功能。结果表明,在新形成的体节中,最初的体节基因MESP2的表达通过主动的细胞分拣机制转化为前部和后部特征的隔间。这项工作表明,参与体节发育的主要模式化模块,包括时钟和波前、AP极性模式化和体节上皮化,可以在这个体外系统中被分离并独立运作。研究人员为启动体节极性模式化的对称性破坏过程定义了一个新的框架。这项工作为解码体节发生的通用原则和推进人类发育的知识提供了一个宝贵的平台。

据了解,脊椎动物的身体显示出一种节段性的组织,这在椎体和周围神经的周期性组织中最为明显。当含有骨骼肌肉和脊椎骨前体的体细胞从前中胚层(PSM)有节律地生成时,这种体节组织首先得以实现。随后,体节被细分为前部和后部,这对脊椎的形成和周围神经系统的节段性形成至关重要。这种关键的体节细分是如何建立的,人们对此了解甚少。

附:英文原文

Title: Reconstruction and deconstruction of human somitogenesis in vitro

Author: Miao, Yuchuan, Djeffal, Yannis, De Simone, Alessandro, Zhu, Kongju, Lee, Jong Gwan, Lu, Ziqi, Silberfeld, Andrew, Rao, Jyoti, Tarazona, Oscar A., Mongera, Alessandro, Rigoni, Pietro, Diaz-Cuadros, Margarete, Song, Laura Min Sook, Di Talia, Stefano, Pourqui, Olivier

Issue&Volume: 2022-12-21

Abstract: The vertebrate body displays a segmental organization which is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric organization is first implemented when somites, which contain the precursors of skeletal muscles and vertebrae, are rhythmically generated from the presomitic mesoderm (PSM). Somites then become subdivided into anterior and posterior compartments essential for vertebral formation and segmental patterning of the peripheral nervous system1–4. How this key somitic subdivision is established remains poorly understood. Here we introduce novel tridimensional culture systems of human pluripotent stem cells (PSCs), called Somitoids and Segmentoids, which recapitulate the formation of somite-like structures with antero-posterior (AP) identity. We identify a key function of the segmentation clock in converting temporal rhythmicity into the spatial regularity of anterior and posterior somitic compartments. We show that an initial salt-and-pepper expression of the segmentation gene MESP2 in the newly formed segment is transformed into compartments of anterior and posterior identity via an active cell sorting mechanism. Our work demonstrates that the major patterning modules involved in somitogenesis including the clock and wavefront, AP polarity patterning and somite epithelialization can be dissociated and operate independently in our in vitro systems. Together we define a novel framework for the symmetry breaking process initiating somite polarity patterning. Our work provides a valuable platform to decode general principles of somitogenesis and advance knowledge of human development.

DOI: 10.1038/s41586-022-05655-4

Source: https://www.nature.com/articles/s41586-022-05655-4

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

分享到:

0