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人類(lèi)胚胎基因表達(dá)始于單細(xì)胞階段

shiguanzhijia 2022-3-25 11:15 試管之家 查看: 648 評(píng)論: 0

摘要:   一項(xiàng)新的研究表明,當(dāng)胚胎剛剛處于單細(xì)胞階段,即受精后,它們就開(kāi)始表現(xiàn)出基因表達(dá)?! ∫郧暗难芯恐荒茉谑芫蟠蠹s兩到三天胚胎長(zhǎng)到四個(gè)或八個(gè)細(xì)胞后才能檢測(cè)到遺傳轉(zhuǎn)錄活性。  “這是對(duì)我們所有人都經(jīng)歷的 ...
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  一項(xiàng)新的研究表明,當(dāng)胚胎剛剛處于單細(xì)胞階段,即受精后,它們就開(kāi)始表現(xiàn)出基因表達(dá)。

  以前的研究只能在受精后大約兩到三天胚胎長(zhǎng)到四個(gè)或八個(gè)細(xì)胞后才能檢測(cè)到遺傳轉(zhuǎn)錄活性。

  “這是對(duì)我們所有人都經(jīng)歷的生物過(guò)程開(kāi)始的第一次良好觀(guān)察——通過(guò)單細(xì)胞胚胎階段的過(guò)渡,”巴斯大學(xué)領(lǐng)導(dǎo)這項(xiàng)研究的研究人員之一托尼佩里教授說(shuō)。.

  由Perry教授、劍橋大學(xué)的Giles Yeo博士和美國(guó)Ovation Fertility的Matthew VerMilyea博士共同領(lǐng)導(dǎo)的一組科學(xué)家使用高分辨率單細(xì)胞RNA測(cè)序來(lái)測(cè)量提供的12個(gè)人類(lèi)*細(xì)胞的基因轉(zhuǎn)錄由七名捐贈(zèng)者和六名不同捐贈(zèng)者提供的12個(gè)人類(lèi)胚胎。

  相反,研究小組發(fā)現(xiàn)胚胎中的基因表達(dá)減少,這些胚胎沒(méi)有繼續(xù)健康發(fā)育,例如由兩個(gè)精子細(xì)胞受精的胚胎,這表明這種早期遺傳活動(dòng)對(duì)于成功發(fā)育至關(guān)重要。“沒(méi)有基因組的覺(jué)醒,發(fā)展就會(huì)失敗,所以這是一個(gè)基本的步驟?!迸謇锝淌诶^續(xù)說(shuō)。

  研究小組發(fā)現(xiàn),雖然在單細(xì)胞胚胎中表達(dá)的基因在二、四和八細(xì)胞階段繼續(xù)表達(dá),但它們的活性在八細(xì)胞階段顯著降低。佩里教授說(shuō):“看起來(lái)早期胚胎中似乎存在某種遺傳轉(zhuǎn)變:第一次轉(zhuǎn)變?cè)谑芫蟛痪瞄_(kāi)始,在單細(xì)胞胚胎中開(kāi)始,第二次轉(zhuǎn)變?cè)诎思?xì)胞階段開(kāi)始?!?/div>

  他們的發(fā)現(xiàn)可能會(huì)導(dǎo)致更好地了解觸發(fā)轉(zhuǎn)錄激活的原因,而這一點(diǎn)尚不為人所知?!半m然人們認(rèn)為激活的觸發(fā)器來(lái)自雞蛋,但不知道是怎么回事;現(xiàn)在我們知道了哪些基因參與其中,我們可以找到它們的地址并使用分子技術(shù)來(lái)找出答案,”佩里教授說(shuō)。

  激活過(guò)程中涉及的一些因素也與癌癥有關(guān),這表明它們可能是觸發(fā)健康胚胎活動(dòng)的原因,而異??赡芎髞?lái)表現(xiàn)為患癌癥的風(fēng)險(xiǎn)。通過(guò)改變受精后的基因激活,表觀(guān)遺傳特征也可能在這個(gè)早期階段從父母?jìng)鹘o孩子。

  “如果屬實(shí),我們應(yīng)該能夠在單細(xì)胞階段看到這種改變的基因激活特征,”Yeo博士建議道。

  該研究發(fā)表在《細(xì)胞干細(xì)胞》雜志上。



  原文:A new study shows that embryos begin to show gene expression when they are just at the single-cell stage,right after fertilisation.

  Previous investigations could only detect genetic transcription activity once the embryo had grown to four or eight cells,around two or three days after fertilisation.

  'This is the first good look at the beginning of a biological process that we all go through–the transit through the one-cell embryo stage,'said Professor Tony Perry,one of the researchers who led the study,at the University of Bath.

  A team of scientists,co-led by Professor Perry,Dr Giles Yeo at the University of Cambridge and Dr Matthew VerMilyea at Ovation Fertility in the USA,used high-resolution single-cell RNA sequencing to measure genetic transcription in 12 human egg cells provided by seven donors and 12 human embryos provided by six different donors.

  Conversely,the team found reduced gene expression in embryos that did not go on to develop healthily,such as those fertilised by two sperm cells,suggesting that this early genetic activity is essential for successful development.'Without genome awakening,development fails,so it's a fundamental step.'Professor Perry continued.

  The team found that while the genes expressed in the single-cell embryo continued to be expressed at the two,four and eight-cell stages,their activity was substantially diminished by eight-cell stage.'It looks as if there is a sort of genetic shift-work in early embryos:the first shift starts soon after fertilisation,in one-cell embryos,and a second shift takes over at the eight-cell stage,'said Professor Perry.

  Their findings may lead to a better understanding of what triggers the activation of transcription,something that is not well-understood.'Although the trigger for activation is thought to come from the egg,it's not known how;now we know which genes are involved,we can locate their addresses and use molecular techniques to find out,'said Professor Perry.

  Some factors involved in the activation process are also associated with cancer,suggesting that they may be responsible for triggering the activity in healthy embryos,while abnormalities could later manifest as a risk of cancer.It is also possible that epigenetic traits,may be passed from parent to child at this early stage,by altering the gene activation after fertilisation.

  'If true,we should be able to see this altered gene activation signature at the one-cell stage,'Dr Yeo suggested.

  The research was published in the journal Cell Stem Cell.

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