Evidence implicating sequential commitment of the founder lineages in the human blastocyst by order of hypoblast gene activation

Evidence implicating sequential commitment of the founder lineages in the human blastocyst by order of hypoblast gene activation
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暗示人类囊胚中创始人谱系按下胚层基因激活顺序顺序定向的证据

DOI:
10.1101/2022.12.08.519626
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发表时间:
2022
期刊:
--
影响因子:
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通讯作者:
Corujo-Simon E
Corujo-Simon E
中科院分区:
--
文献类型:
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作者:
Corujo-Simon E

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成功的人类妊娠取决于三个创始谱系的快速建立:滋养外胚层、上胚层和下胚层,它们共同形成胚泡。每一个都在胚胎植入和随后的发育中起着至关重要的作用。已经提出了几种模型来定义谱系隔离。一种观点认为,所有谱系都是同时指定的;另一种观点认为,在上胚细胞和下胚细胞分离之前,滋养外胚层会分化,要么通过下胚细胞从已建立的上胚细胞分化,要么通过内细胞团前体产生两种组织。为了开始解决这种差异,从而了解生产可行的人类胚胎的顺序过程,我们研究了与下胚层出现相关的基因的表达顺序。基于已发表的数据和候选基因的免疫荧光分析,我们提出了一个基本的蓝图,人类下胚层分化,贷款支持所提出的模型的创始人谱系的人类囊胚的顺序分离。最初特异于早期内细胞团并随后鉴定推定的下胚层的第一个特征性标志物是PDGFRA,随后是SOX 17、FOXA 2和GATA 4,随着下胚层定型。
Successful human pregnancy depends upon rapid establishment of three founder lineages: the trophectoderm, epiblast and hypoblast, which together form the blastocyst. Each plays an essential role in preparing the embryo for implantation and subsequent development. Several models have been proposed to define the lineage segregation. One suggests that all lineages specify simultaneously; another favours the differentiation of the trophectoderm before separation of the epiblast and hypoblast, either via differentiation of the hypoblast from the established epiblast, or production of both tissues from the inner cell mass precursor. To begin to resolve this discrepancy and thereby understand the sequential process for production of viable human embryos, we investigated the expression order of genes associated with emergence of hypoblast. Based upon published data and immunofluorescence analysis for candidate genes, we present a basic blueprint for human hypoblast differentiation, lending support to the proposed model of sequential segregation of the founder lineages of the human blastocyst. The first characterised marker, specific initially to the early inner cell mass, and subsequently identifying presumptive hypoblast, is PDGFRA, followed by SOX17, FOXA2 and GATA4 in sequence as the hypoblast becomes committed.