对来自原肠胚的人类胚胎进行了高分辨率的单细胞基因表达分析,提供了突破性的见解。
由于人类胚胎在英国不能合法地培养超过14天,如果科学家想研究它们,它们必须是自然受孕和终止后捐赠的。由于大多数潜在的捐赠者不知道他们在这个阶段怀孕,因此不寻求堕胎,对原肠道阶段和此后不久(受精后约两周)的人类胚胎的研究极为罕见。
牛津大学教授、该研究的通讯作者Shankar Srinivas说:"我们的身体是由数百种细胞类型组成的。正是在这个阶段,为在我们体内产生大量的细胞奠定了基础--细胞类型的多样性爆炸。
这项研究发表在《自然》杂志上,由牛津大学和慕尼黑亥姆霍兹中心的研究人员进行,重点是受精后16-19天的单一捐赠者胚胎。研究人员将胚胎解剖成单个细胞,并对总共1195个单个细胞的信使RNA进行了测序,以建立一个所有细胞类型的非常详细的基因表达谱。
获得控制这一发育步骤的分子机制的高分辨率数据尤为重要。这是一个相对不确定数量的细胞开始分化为身体不同部分的时间点。
进步教育信托基金主任萨拉-诺克罗斯说:"研究人员在这个16-19天的阶段拥有人类胚胎的样本是极其罕见的。在可预见的未来,这种情况不太可能再次发生,这使得这项研究更有价值,也是延长14天规则的另一个论据,以允许在实验室使用培养物进行超过14天的研究。
这项工作为从干细胞到指定人体组织类型的途径提供了一个更完整的图景。这种更好的理解在治疗和诊断发育疾病以及体外培养人体组织和器官方面可能是有用的。
这些结果也突出了人类和模式生物在胚胎发育这一阶段的相似性。牛津大学的Richard Teather博士和该研究的主要作者说:"令人欣慰的是,我们现在已经能够证明小鼠确实在分子水平上模仿人类的发展。这样的模型已经提供了宝贵的见解,但这项研究现在可以进一步丰富,因为我们能够将光线投射到这个黑匣子里,更仔细地观察它在人类中的工作情况。
然而,在这项工作中发现的机制与发生在其他动物身上的机制仍有许多不同之处。这些结果强调了研究人类胚胎发育的这一步骤的重要性,以及它可能对科学进步造成的障碍。
诺克罗斯总结说:"如果14天的规则被延长,这项研究将提供一个有价值的参考点,以更好地理解和说明在体外和体内生长的胚胎之间的相似性和差异。" "在这里,我们有机会打开人类发育的'黑匣子',研究原生胚胎的形成和相关过程,提高我们对疾病和治疗的认识,也许还能提高我们对流产和不孕的认识。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
Early stage of human embryonic development visible for the first time
A high-resolution single-cell gene expression analysis has been performed on a human embryo at the gastrulation stage, providing groundbreaking insights.
Because human embryos cannot legally be cultured for more than 14 days in the United Kingdom, if scientists want to study them, they must be conceived naturally and donated after an abortion. Since most potential donors do not know they are pregnant at this stage and therefore do not wish to terminate their pregnancy, studies of human embryos in the gastrulation phase and shortly thereafter, which occurs about two weeks after fertilization, are extremely rare.
Professor Shankar Srinivas of the University of Oxford and lead author of the study said: "Our bodies are made up of hundreds of cell types, and it is at this stage that the foundation is laid for the emergence of the huge diversity of cells in our bodies - it is like an explosion of diversity of cell types.
The study, published in Nature and conducted by researchers at the University of Oxford and Helmholtz Zentrum München, focused on a single donated embryo created 16-19 days after fertilization. The researchers separated the embryo into its individual cells and sequenced messenger RNA from a total of 1195 individual cells to create a highly detailed map of gene expression in the different cell types.
Obtaining high-resolution data on the molecular mechanisms controlling this developmental step is particularly important because it is at this point that a collection 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 researchers to have specimens of human embryos at this 16- to 19-day stage. The fact that this is unlikely to be the case in the foreseeable future makes this study all the more valuable and argues for an extension of the 14-day rule so that early human development can be better understood by studying embryos cultured in the laboratory beyond 14 days.
The work has provided a more comprehensive picture of the pathway from stem cell to tissue type specification in humans. This improved understanding could aid in the treatment and diagnosis of developmental diseases and efforts to grow human tissues and organs outside the body.
Dr. Richard Tyser of Oxford University and lead author of the study said, "It is reassuring that we have now been able to show that the mouse is a model for human development at the molecular level. Such models were already providing valuable insights, but now we can enrich this research further by shedding light on this black box and seeing in more detail how it works in humans.
The results highlight the importance of studying this step of embryogenesis in humans and the impact that obstacles to doing so can have on scientific progress.
Norcross concludes, "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 accounted for. We have an opportunity here to open the "black box" of human development, to study gastrulation and related processes, to improve our understanding and treatment of disease, and perhaps to improve our understanding of miscarriage and infertility.
Others also stressed the importance and significance of the study. "The new study is a game changer for developmental biologists," said Dr. Peter Rugg-Gunn of the Babraham Institute in Cambridge, who was not involved in the study. "The new study is already providing important new insights into how early cell lineages are formed and positioned in the developing embryo.... This information provides new clues to understanding why these processes sometimes go awry during pregnancy, which can lead to developmental problems in some babies.