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Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development

机译:干细胞集落和早期哺乳动物胚胎的自组织:最近的实验为自主与外部指令在基本人体计划制定中的作用提供了新的思路

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摘要

“Organoids”, i.e., complex structures that can develop when pluripotent or multipotent stem cells are maintained in three-dimensional cultures, have become a new area of interest in stem cell research. Hopes have grown that when focussing experimentally on the mechanisms behind this type of in vitro morphogenesis, research aiming at tissue and organ replacements can be boosted. Processes leading to the formation of organoids in vitro are now often addressed as self-organization, a term referring to the formation of complex tissue architecture in groups of cells without depending on specific instruction provided by other cells or tissues. The present article focuses on recent reports using the term self-organization in the context of studies on embryogenesis, specifically addressing pattern formation processes in human blastocysts attaching in vitro, or in colonies of pluripotent stem cells (“gastruloids”). These morphogenetic processes are of particular interest because, during development in vivo, they lead to basic body plan formation and individuation. Since improved methodologies like those employed by the cited authors became available, early embryonic pattern formation/self-organization appears to evolve now as a research topic of its own. This review discusses concepts concerning the involved mechanisms, focussing on autonomy of basic body plan development vs. dependence on external signals, as possibly provided by implantation in the uterus, and it addresses biological differences between an early mammalian embryo, e.g., a morula, and a cluster of pluripotent stem cells. It is concluded that, apart from being of considerable biological interest, the described type of research needs to be contemplated carefully with regard to ethical implications when performed with human cells.
机译:当在三维培养物中维持多能或多能干细胞时,可能会形成的“有机物”即复杂结构已成为干细胞研究中的一个新领域。越来越多的希望是,当将实验重点放在这类体外形态发生的机制上时,可以促进针对组织和器官置换的研究。现在,导致体外类器官形成的过程通常被称为自组织,该术语是指在不依赖于其他细胞或组织提供的特定指令的情况下,在细胞组中形成复杂的组织结构的过程。本文重点关注在胚胎发生研究的背景下使用“自组织”一词的最新报道,特别是针对体外附着的人胚泡或多能干细胞(“类胚体”)集落中的模式形成过程。这些形态发生过程特别受关注,因为它们在体内发育过程中会导致基本的人体计划形成和个体化。由于像被引用的作者所采用的那样的改进方法变得可用,因此早期的胚胎模式形成/自组织似乎已经发展成为其自身的研究主题。这篇综述讨论了有关涉及机制的概念,着重于基本人体计划制定的自主性与对外部信号的依赖性(可能是通过植入子宫所提供的),并探讨了早期哺乳动物胚胎(如桑ula鱼)之间的生物学差异。一簇多能干细胞。结论是,除了具有相当大的生物学意义外,在与人类细胞一起进行研究时,还需要仔细考虑所研究类型的伦理意义。

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