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人类胚胎发育的早期阶段首次出现

游海 2021-12-28 11:54 试管之家 查看: 55 评论: 0

摘要:   已对原肠胚形成的人类胚胎进行了高分辨率单细胞基因表达分析,提供了具有里程碑意义的见解。  由于人类胚胎在英国的合法培养时间不能超过14天,如果科学家希望研究它们,胚胎必须自然受孕并在终止后捐赠。由于 ...
  已对原肠胚形成的人类胚胎进行了高分辨率单细胞基因表达分析,提供了具有里程碑意义的见解。

  由于人类胚胎在英国的合法培养时间不能超过14天,如果科学家希望研究它们,胚胎必须自然受孕并在终止后捐赠。由于大多数潜在捐赠者不知道他们在这个阶段怀孕,因此不会寻求终止,因此对处于原肠胚形成阶段及其后不久的人类胚胎进行的研究极为罕见,该阶段发生在受精后两周左右。

  牛津大学教授、该研究的通讯作者Shankar Srinivas说:“我们的身体由数百种细胞组成。正是在这个阶段,为我们体内产生大量细胞奠定了基础——就像细胞类型多样性的爆炸式增长。

  该研究发表在《自然》杂志上,由牛津大学和德国慕尼黑亥姆霍兹中心的研究人员进行,重点是在受精后16-19天进行的单个捐赠胚胎。研究人员将胚胎分成其组成细胞,对总共1195个单个细胞的信使RNA进行测序,以创建跨细胞类型的高度详细的基因表达图谱。

  生成控制这一发展步骤的分子机制的高分辨率数据尤其重要。这是一组相对不确定的细胞开始分化成身体不同部位的点。

  进步教育信托基金的负责人莎拉·诺克罗斯说:“在这个16-19天阶段的人类胚胎标本可供研究人员使用是极其罕见的。在可预见的未来这种情况不太可能再次发生的事实使这项研究更加宝贵,并增加了延长14天规则的理由,以便通过研究具有在实验室培养超过14天。

  这项工作提供了从干细胞到人类组织类型规范的路径的更全面图景。这种增强的理解可以为发育性疾病的治疗和诊断以及在体外培养人体组织和器官的努力提供信息。

  结果还揭示了人类和模型研究生物在胚胎发生的这个阶段之间的相似性。牛津大学的理查德·泰瑟博士和该论文的第一作者说:“令人欣慰的是,我们现在已经能够证明小鼠确实模拟了人类在分子水平上的发育方式。这样的模型已经提供了有价值的见解,但现在这项研究可以进一步丰富,因为我们能够将光投射到那个黑匣子中,并更仔细地观察它在人类中是如何工作的。

  然而,这项工作揭示的机制与其他动物发生的机制之间仍然存在许多差异。研究结果强调了研究人类胚胎发生这一步骤的重要性,以及这可能对科学进步产生的影响障碍。

  诺克罗斯总结道:“如果延长14天规则,这项研究将提供一个宝贵的参考点,以便更好地理解和考虑体外和体内培养的胚胎之间的异同。”我们在这里有机会打开人类发展的“黑匣子”,研究原肠胚形成和相关过程,提高我们对疾病的理解和治疗,或许也能提高我们对流产和不孕症的理解。我们应该抓住这个机会。

  其他人也热衷于强调这项研究的重要性和意义。“这项新研究为发育生物学家提供了罗塞塔石碑,”剑桥Babraham研究所的Peter Rugg-Gunn博士说,他没有参与这项研究。'这项新研究已经对早期细胞谱系如何在发育中的胚胎中形成和定位产生了重要的新见解......这些信息提供了新的线索,以了解为什么这些过程有时会在怀孕期间出错,从而导致发育缺陷一些婴儿。

以下原文:

  Early stage of human embryo development seen for the first time

  High-resolution single-cell gene expression analysis has been performed on a gastrulating human embryo,providing landmark insights.

  Because human embryos cannot legally be cultured longer than 14 days in the UK,if scientists wish to study them the embryos must be conceived naturally and donated following a termination.As most potential donors do not know they are pregnant at this stage and so would not be seeking termination,studies on human embryos at and shortly beyond a phase known as gastrulation,which occurs around two weeks after fertilisation,are extremely rare.

  Professor Shankar Srinivas of the University of Oxford and corresponding author of the study said:'Our body is made up of hundreds of types of cells.It is at this stage that the foundation is laid for generating the huge variety of cells in our body–it's like an explosion of diversity of cell types.'

  The study,published in Nature and performed by researchers at the University of Oxford and the Helmholtz Zentrum München,Germany,focused on a single donated embryo staged at 16–19 days post-fertilisation.Researchers separated the embryo into its constituent cells,sequencing the messenger RNA of a total of 1195 individual cells to create a highly detailed map of gene expression across cell types.

  Generation of high-resolution data of the molecular mechanisms governing this step of development is especially crucial.This is the point at which a cluster of relatively indeterminate cells begins to differentiate into different parts of the body.

  Sarah Norcross,director of the Progress Educational Trust,said:'It is extremely rare for specimens of human embryos at this 16–19 day stage to become available to researchers.The fact that this is unlikely to happen again in the foreseeable future makes this study all the more precious,and adds to the case for extending the 14-day rule,so that early human development can be better understood through the study of embryos that have been cultured in the laboratory beyond 14 days.'

  The work has provided a fuller picture of the path from stem cell to tissue type specification in humans.This enhanced understanding could inform treatment and diagnosis of developmental diseases and efforts to grow human tissues and organs outside the body.

  The results have also revealed similarities between humans and model research organisms at this stage of embryogenesis.Dr Richard Tyser of the University of Oxford and first author of the paper said:'Reassuringly,we have now been able to show that the mouse does model how a human develops at the molecular level.Such models were already providing valuable insights,but now this research can be further enriched by the fact we're able to cast light into that black box and more closely see how it works in humans.'

  However,many differences remain between the mechanisms revealed by this work and those which take place in other animals.The findings highlight the importance of studying this step of embryogenesis in humans and the effect barriers to this may have on scientific progress.

  Norcross concluded:'If and when the 14-day rule is extended,this study will provide an invaluable reference point,so that similarities and differences between embryos cultured in vitro and in vivo can be better understood and taken into account.We have an opportunity here to open the"black box"of human development,study gastrulation and related processes,improve our understanding and treatment of disease,and perhaps improve our understanding of miscarriage and infertility as well.We should seize this opportunity.'

  Others were keen to emphasise the importance and significance of the study too.'The new study provides a Rosetta Stone for developmental biologists,'Dr Peter Rugg-Gunn,of the Babraham Institute,in Cambridge said who was not involved in the study.'The new study is already yielding important new insights into how the early cell lineages are formed and positioned in the developing embryo...This information provides new leads to understand why these processes sometimes go wrong during pregnancy,which can result in developmental defects in some babies.'

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