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单细胞和空间转录组揭示类原肠胚的体节发生
作者:小柯机器人 发布时间:2020/3/3 11:31:58

荷兰乌得勒支大学医学中心Alexander van Oudenaarden、Susanne C. van den Brink等研究人员合作利用单细胞和空间转录组揭示了类原肠胚的体节发生。相关论文于2020年2月19日在线发表在《自然》杂志上。

研究人员使用单细胞RNA测序和空间转录组学来比较了小鼠类原肠胚与小鼠胚胎。他们确定了各种以前未知的类原肠胚细胞类型,并表明在胚胎和类原肠胚之间相似地表达了体节发生的关键调控因子。使用实时成像,研究人员表明体节发生时钟活跃在类原肠胚中,并具有类似于体内的动态。因为类原肠胚可以大量生长,所以他们进行了一个小型筛选,从而揭示了降低的FGF信号如何诱导胚胎中的短尾表型。最后,研究人员证明了在基质胶中包埋会诱导类原肠胚产生具有正确头尾模式的体节,随着时间沿前后方向依次出现。因此,这项研究显示了类原肠胚作为模型系统的能力,其能够以高通量方式研究体外发育和体节发生。
 
据了解,类原肠胚是胚胎干细胞的三维聚集体,在着床后表现出哺乳动物发育的关键特征,包括胚层分化和轴向形成。目前,人们已经利用显微镜研究了类原肠胚中少数基因的表达模式,并且尚不清楚在类原肠胚在模拟胚胎时全基因组表达模式到达何种程度。
 
附:英文原文

Title: Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids

Author: Susanne C. van den Brink, Anna Alemany, Vincent van Batenburg, Naomi Moris, Marloes Blotenburg, Judith Vivi, Peter Baillie-Johnson, Jennifer Nichols, Katharina F. Sonnen, Alfonso Martinez Arias, Alexander van Oudenaarden

Issue&Volume: 2020-02-19

Abstract: Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization1,2,3. To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral–caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.

DOI: 10.1038/s41586-020-2024-3

Source: https://www.nature.com/articles/s41586-020-2024-3

期刊信息

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