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人類胚胎發(fā)育的早期階段首次出現(xiàn)

游海 2021-12-21 11:54 試管之家 查看: 597 評(píng)論: 0

摘要:   已對(duì)原腸胚形成的人類胚胎進(jìn)行了高分辨率單細(xì)胞基因表達(dá)分析,提供了具有里程碑意義的見(jiàn)解?! ∮捎谌祟惻咛ピ谟?guó)的合法培養(yǎng)時(shí)間不能超過(guò)14天,如果科學(xué)家希望研究它們,胚胎必須自然受孕并在終止后捐贈(zèng)。由于 ...
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  已對(duì)原腸胚形成的人類胚胎進(jìn)行了高分辨率單細(xì)胞基因表達(dá)分析,提供了具有里程碑意義的見(jiàn)解。

  由于人類胚胎在英國(guó)的合法培養(yǎng)時(shí)間不能超過(guò)14天,如果科學(xué)家希望研究它們,胚胎必須自然受孕并在終止后捐贈(zèng)。由于大多數(shù)潛在捐贈(zèng)者不知道他們?cè)谶@個(gè)階段懷孕,因此不會(huì)尋求終止,因此對(duì)處于原腸胚形成階段及其后不久的人類胚胎進(jìn)行的研究極為罕見(jiàn),該階段發(fā)生在受精后兩周左右。

  牛津大學(xué)教授、該研究的通訊作者Shankar Srinivas說(shuō):“我們的身體由數(shù)百種細(xì)胞組成。正是在這個(gè)階段,為我們體內(nèi)產(chǎn)生大量細(xì)胞奠定了基礎(chǔ)——就像細(xì)胞類型多樣性的爆炸式增長(zhǎng)。

  該研究發(fā)表在《自然》雜志上,由牛津大學(xué)和德國(guó)慕尼黑亥姆霍茲中心的研究人員進(jìn)行,重點(diǎn)是在受精后16-19天進(jìn)行的單個(gè)捐贈(zèng)胚胎。研究人員將胚胎分成其組成細(xì)胞,對(duì)總共1195個(gè)單個(gè)細(xì)胞的信使RNA進(jìn)行測(cè)序,以創(chuàng)建跨細(xì)胞類型的高度詳細(xì)的基因表達(dá)圖譜。

  生成控制這一發(fā)展步驟的分子機(jī)制的高分辨率數(shù)據(jù)尤其重要。這是一組相對(duì)不確定的細(xì)胞開(kāi)始分化成身體不同部位的點(diǎn)。

  進(jìn)步教育信托基金的負(fù)責(zé)人莎拉·諾克羅斯說(shuō):“在這個(gè)16-19天階段的人類胚胎標(biāo)本可供研究人員使用是極其罕見(jiàn)的。在可預(yù)見(jiàn)的未來(lái)這種情況不太可能再次發(fā)生的事實(shí)使這項(xiàng)研究更加寶貴,并增加了延長(zhǎng)14天規(guī)則的理由,以便通過(guò)研究具有在實(shí)驗(yàn)室培養(yǎng)超過(guò)14天。

  這項(xiàng)工作提供了從干細(xì)胞到人類組織類型規(guī)范的路徑的更全面圖景。這種增強(qiáng)的理解可以為發(fā)育性疾病的治療和診斷以及在體外培養(yǎng)人體組織和器官的努力提供信息。

  結(jié)果還揭示了人類和模型研究生物在胚胎發(fā)生的這個(gè)階段之間的相似性。牛津大學(xué)的理查德·泰瑟博士和該論文的第一作者說(shuō):“令人欣慰的是,我們現(xiàn)在已經(jīng)能夠證明小鼠確實(shí)模擬了人類在分子水平上的發(fā)育方式。這樣的模型已經(jīng)提供了有價(jià)值的見(jiàn)解,但現(xiàn)在這項(xiàng)研究可以進(jìn)一步豐富,因?yàn)槲覀兡軌驅(qū)⒐馔渡涞侥莻€(gè)黑匣子中,并更仔細(xì)地觀察它在人類中是如何工作的。

  然而,這項(xiàng)工作揭示的機(jī)制與其他動(dòng)物發(fā)生的機(jī)制之間仍然存在許多差異。研究結(jié)果強(qiáng)調(diào)了研究人類胚胎發(fā)生這一步驟的重要性,以及這可能對(duì)科學(xué)進(jìn)步產(chǎn)生的影響障礙。

  諾克羅斯總結(jié)道:“如果延長(zhǎng)14天規(guī)則,這項(xiàng)研究將提供一個(gè)寶貴的參考點(diǎn),以便更好地理解和考慮體外和體內(nèi)培養(yǎng)的胚胎之間的異同?!蔽覀?cè)谶@里有機(jī)會(huì)打開(kāi)人類發(fā)展的“黑匣子”,研究原腸胚形成和相關(guān)過(guò)程,提高我們對(duì)疾病的理解和治療,或許也能提高我們對(duì)流產(chǎn)和不孕癥的理解。我們應(yīng)該抓住這個(gè)機(jī)會(huì)。

  其他人也熱衷于強(qiáng)調(diào)這項(xiàng)研究的重要性和意義?!斑@項(xiàng)新研究為發(fā)育生物學(xué)家提供了羅塞塔石碑,”劍橋Babraham研究所的Peter Rugg-Gunn博士說(shuō),他沒(méi)有參與這項(xiàng)研究。'這項(xiàng)新研究已經(jīng)對(duì)早期細(xì)胞譜系如何在發(fā)育中的胚胎中形成和定位產(chǎn)生了重要的新見(jiàn)解......這些信息提供了新的線索,以了解為什么這些過(guò)程有時(shí)會(huì)在懷孕期間出錯(cuò),從而導(dǎo)致發(fā)育缺陷一些嬰兒。

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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