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Nature揭示减数分裂的守护者

标签:减数分裂
摘要 : 已知人类卵母细胞的减数分裂是很容易出错的,而卵子缺陷是导致妊娠丢失(pregnancy loss)和一些严重遗传疾病(比如唐氏综合症)的主要原因。那么,是谁在为减数分裂的顺利进行保驾护航呢?

 在受精过程中,卵子和精子融和生成新的胚胎。卵子和精子都是通过减数分裂形成的,细胞在减数分裂时连续分裂两次,而基因组只复制一次。结果是,精细胞和卵细胞各获得一半的亲代染色体。

已知人类卵母细胞的减数分裂是很容易出错的,而卵子缺陷是导致妊娠丢失(pregnancy loss)和一些严重遗传疾病(比如唐氏综合症)的主要原因。那么,是谁在为减数分裂的顺利进行保驾护航呢?

世界顶级研究机构,英国医学研究委员会(MRC)分子生物学实验室的研究团队对此进行了深入研究。他们开发了一个高内涵的表型筛选方法,全面鉴定了哺乳动物卵母细胞中的减数分裂基因。这项研究发表在七月六日的Nature杂志上,文章的通讯作这是MRC 的Melina Schuh。

与有丝分裂相比,人们对减数分裂的了解还比较少。系统性筛选是认识有丝分裂基因的有力武器,但这一技术用于哺乳动物减数分裂时还存在一些问题。

研究人员将小鼠卵母细胞的表达谱与其他体细胞以及植入前胚胎进行比较,选出了在卵母细胞高度表达但不参与胚胎发育的774个基因,并且构建了靶标这些基因的siRNA。

为了获得高通量,研究人员决定一次靶标12个基因,然后通过高分辨率成像分析这些基因的功能。他们通过显微注射把混合siRNA送入包裹在卵泡里的卵母细胞,在卵母细胞发育的早期阶段阻断蛋白质表达。然后对卵泡进行体外培养,等卵母细胞长大之后将其分离出来。

研究人员通过共聚焦显微镜的活细胞成像,观察了大量卵母细胞的减数分裂过程。他们定量分析了卵母细胞的50种表型,获得了丰富的减数分裂数据,并在此基础上鉴定了一些关键的基因,比如Dusp7。

这项研究为人们提供了适合卵母细胞的高内涵筛选方法,可以帮助人们全面理解哺乳动物的减数分裂。

推荐原文:Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes

原文标题:During fertilization, an egg and a sperm fuse to form a new embryo. Eggs develop from oocytes in a process called meiosis. Meiosis in human oocytes is highly error-prone1, 2, and defective eggs are the leading cause of pregnancy loss and several genetic disorders such as Down’s syndrome3, 4, 5. Which genes safeguard accurate progression through meiosis is largely unclear. Here we develop high-content phenotypic screening methods for the systematic identification of mammalian meiotic genes. We targeted 774 genes by RNA interference within follicle-enclosed mouse oocytes to block protein expression from an early stage of oocyte development onwards. We then analysed the function of several genes simultaneously by high-resolution imaging of chromosomes and microtubules in live oocytes and scored each oocyte quantitatively for 50 phenotypes, generating a comprehensive resource of meiotic gene function. The screen generated an unprecedented annotated data set of meiotic progression in 2,241 mammalian oocytes, which allowed us to analyse systematically which defects are linked to abnormal chromosome segregation during meiosis, identifying progression into anaphase with misaligned chromosomes as well as defects in spindle organization as risk factors. This study demonstrates how high-content screens can be performed in oocytes, and allows systematic studies of meiosis in mammals.

来源: Nature 浏览次数:0

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