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人类滋养层和胚胎干细胞衍生滋养层的比较转录组分析揭示了早期植入的关键参与者。

Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation.

机构信息

Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, USA.

出版信息

Biol Reprod. 2012 Jan 16;86(1):1-21. doi: 10.1095/biolreprod.111.092775. Print 2012 Jan.

DOI:10.1095/biolreprod.111.092775
PMID:21865555
Abstract

The implantation process begins with attachment of the trophectoderm (TE) of the blastocyst to the maternal endometrial epithelium. Herein we have investigated the transcriptome of mural TE cells from 13 human blastocysts and compared these with those of human embryonic stem cell (hESC)-derived-TE (hESC(troph)). The transcriptomes of hESC(troph) at Days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted proteins of the TE of human blastocysts and of hESC(troph) are several molecules known to be involved in the implantation process, as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, WNT5A, and follistatin. The similarities between the two lineages underscore some of the known mechanisms and offer discovery of new mechanisms and players in the process of the very early stages of human implantation. We propose that the hESC(troph) is a viable functional model of human trophoblasts to study trophoblast-endometrial interactions. Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics aimed at practical challenges in human infertility and pregnancy disorders associated with abnormal embryonic implantation.

摘要

胚胎植入过程始于囊胚的滋养外胚层(TE)附着到母体子宫内膜上皮。在此,我们研究了 13 个人类囊胚的壁滋养层细胞的转录组,并将其与人类胚胎干细胞(hESC)衍生的滋养层(hESC(troph))进行了比较。hESC(troph)在第 8、10 和 12 天的转录组与 TE 的一致性最大。在编码人类囊胚和 hESC(troph)的 TE 分泌蛋白的基因中,有几个已知参与着床过程的分子,以及一些新的分子,如 CXCL12、HBEGF、抑制素 A、DKK3、WNT5A 和卵泡抑素。这两个谱系之间的相似性强调了一些已知的机制,并为人类着床早期阶段的新机制和参与者的发现提供了机会。我们提出 hESC(troph)是研究滋养层-子宫内膜相互作用的可行的人类滋养层功能模型。此外,本文提供的资料有望开发出针对与异常胚胎着床相关的人类不育和妊娠障碍的实用挑战的新型诊断和治疗方法。

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