小柯机器人

体外表征人类的分节时钟
2020-01-10 14:28

近日,美国哈佛医学院Olivier Pourqui及其研究小组的最新研究在体外表征了人类的分节时钟。该研究于2020年1月8日在线发表于国际一流学术期刊《自然》。

研究人员发现,体外产生的人类前体节中胚层(PSM)细胞(以及小鼠的)重现了分节时钟的振荡。人PSM细胞的振荡周期是小鼠细胞的两倍(5小时与2.5小时),但同样受到FGF、WNT、Notch和YAP信号的调节。单细胞RNA测序揭示了小鼠和人的体外PSM细胞遵循与小鼠体内PSM类似的发育轨迹。此外,研究人员证明了FGF信号控制振荡的相位和周期,使该途径的作用延伸到了“时钟和波前”模型中的经典解释之外。研究人员发现的人类分节时钟代表了理解人类发育生物学的重要里程碑。

研究人员表示,脊柱的分节组织是在胚胎发生的早期建立的,这时成对的体节由PSM有节奏地产生。体节形成的速度由称为分节时钟的分子振荡因子控制。尽管这种振荡因子已经在模型生物中得到了很好的表征,但尚不清楚人类中是否存在类似的振荡因子。对具有严重脊柱节段缺损的患者进行的遗传分析表明,几种人类周期基因的同源物与小鼠分节时钟相关,从而表明这一振荡因子在人类中可能是保守的。

附:英文原文

Title: In vitro characterization of the human segmentation clock

Author: Margarete Diaz-Cuadros, Daniel E. Wagner, Christoph Budjan, Alexis Hubaud, Oscar A. Tarazona, Sophia Donelly, Arthur Michaut, Ziad Al Tanoury, Kumiko Yoshioka-Kobayashi, Yusuke Niino, Ryoichiro Kageyama, Atsushi Miyawaki, Jonathan Touboul, Olivier Pourqui

Issue&Volume: 2020-01-08

Abstract: The segmental organization of the vertebral column is established early in embryogenesis, when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock1,2. Although this oscillator has been well-characterized in model organisms1,2, whether a similar oscillator exists in humans remains unknown. Genetic analyses of patients with severe spine segmentation defects have implicated several human orthologues of cyclic genes that are associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans3. Here we show that human PSM cells derived in vitroas well as those of the mouse4recapitulate the oscillations of the segmentation clock. Human PSM cells oscillate with a period two times longer than that of mouse cells (5 h versus 2.5 h), but are similarly regulated by FGF, WNT, Notch and YAP signalling5. Single-cell RNA sequencing reveals that mouse and human PSM cells in vitro follow a developmental trajectory similar to that of mouse PSM in vivo. Furthermore, we demonstrate that FGF signalling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in clock and wavefront models1. Our work identifying the human segmentation clock represents an important milestone in understanding human developmental biology. Human presomitic mesoderm cells derived in vitro demonstrate oscillations of the segmentation clock, thus providing a window into an otherwise inaccessible stage of human development.

DOI: 10.1038/s41586-019-1885-9

Source: https://www.nature.com/articles/s41586-019-1885-9

 

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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