小柯机器人

科学家首次在体实现着床后期的小鼠胚胎发生
2021-03-21 12:59

以色列魏茨曼科学研究所Jacob H. Hanna等研究人员合作实现从原肠运动前到晚期器官发生的子宫外小鼠胚胎发生。相关论文于2021年3月17日在线发表于国际学术期刊《自然》。

研究人员开发了高度有利于子宫外着床后小鼠胚胎培养的平台,该平台能够在原肠运动前(E5.5)直到后肢形成阶段(E11)进行适当的胚胎发育。晚期原肠胚化的胚胎(E7.5)在3D旋转瓶中生长,而从怀孕前阶段(E5.5或E6.5)进行的扩增培养需要结合使用新颖的静态瓶和旋转瓶培养平台。组织学、分子和单细胞RNA-seq分析验证了子宫外培养的胚胎在子宫内发育过程中的精确再现。

这种培养系统适合引入多种胚胎扰动和显微操作,这些干扰和离体操作可以在子宫外进行长达六天。这个系统的建立是研究胚胎发生的重要工具,子宫外正常小鼠的胚胎从怀孕前到晚期器官发生过程都能够健壮地生长,这个系统消除了对哺乳动物着床后形态发生和组织成型进行机制研究的子宫壁垒。 

据介绍,在胚胎着床于母体子宫后不久,哺乳动物的身体计划就建立了,而人们对着床后发育过程的了解仍然有限。虽然通常采用着床前和着床前后小鼠胚胎的体外培养方法,但仍需要建立从卵圆柱阶段培养着床后胚胎直至成熟器官发生的方法。

附:英文原文

Title: Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis

Author: Alejandro Aguilera-Castrejon, Bernardo Oldak, Tom Shani, Nadir Ghanem, Chen Itzkovich, Sharon Slomovich, Shadi Tarazi, Jonathan Bayerl, Valeriya Chugaeva, Muneef Ayyash, Shahd Ashouokhi, Daoud Sheban, Nir Livnat, Lior Lasman, Sergey Viukov, Mirie Zerbib, Yoseph Addadi, Yoach Rais, Saifeng Cheng, Yonatan Stelzer, Hadas Keren-Shaul, Raanan Shlomo, Rada Massarwa, Noa Novershtern, Itay Maza, Jacob H. Hanna

Issue&Volume: 2021-03-17

Abstract: Establishment of the mammalian body plan occurs shortly after the embryo implants into the maternal uterus, and our understanding of post-implantation developmental processes remains limited. While methods for in vitro culture of pre- and peri-implantation mouse embryos are routinely utilized1,2, approaches for robust culture of post-implantation embryos from egg cylinder stages until advanced organogenesis remain to be established. Here we develop highly conducive ex utero post-implantation mouse embryo culture platforms, that enable appropriate development of embryos before gastrulation (E5.5) until the hind limb formation stage (E11). Late gastrulating embryos (E7.5) are grown in 3D rotating bottles settings, while extended culture from pre-gastrulation stages (E5.5 or E6.5) requires a combination of novel static and rotating bottle culture platforms. Histological, molecular, and single-cell RNA-seq analyses validate that the ex utero cultured embryos recapitulate in utero development precisely. This culture system is amenable to introducing a variety of embryonic perturbations and micro-manipulations that can be followed ex utero for up to six days. Establishment of a system to robustly grow normal mouse embryos ex utero from pre-gastrulation to advanced organogenesis represents a valuable tool to investigate embryogenesis, eliminating the uterine barrier to mechanistically interrogate post-implantation morphogenesis and tissue specification in mammals.

DOI: 10.1038/s41586-021-03416-3

Source: https://www.nature.com/articles/s41586-021-03416-3

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

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