Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation.
Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation.
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DOI：
10.1038/ncomms11958
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发表时间：
2016-06-15
影响因子：
16.6
通讯作者：
Antonyak MA
中科院分区：
文献类型：
--
作者：
Desrochers LM;Bordeleau F;Reinhart-King CA;Cerione RA;Antonyak MA
已知胚泡的内细胞团（ICM）和滋养层之间存在通讯，但其对早期发育事件的功能影响尚不清楚。在此我们证明，源自内细胞团的胚胎干细胞（ES）会产生并释放微泡（MVs），这是细胞外囊泡（EVs）的一个主要类别，它会在着床过程中影响滋养层的行为。微泡携带的层粘连蛋白和纤连蛋白与滋养层表面的整合素相互作用，触发两种信号激酶JNK和FAK的激活，并刺激滋养层迁移。我们进一步表明，将从胚胎干细胞中分离出的微泡注射到胚泡中会提高其着床效率。因此，这些发现凸显了一种独特的机制，通过该机制胚胎干细胞与胚泡内的滋养层进行通讯，以提高其迁移到子宫的能力，从而促进妊娠期间最早且最重要的步骤之一。
胚胎干细胞（ESC）在着床过程中如何与周围细胞通讯尚不清楚。在此，作者表明胚胎干细胞会释放微泡，激活滋养层中的整合素以及JNK/FAK激酶，在体外刺激迁移，并且注射微泡可提高胚泡着床率。
Communication between the inner cell mass (ICM) and the trophoblast layer of the blastocyst is known to occur, but its functional consequences on early developmental events is unclear. Here we demonstrate that embryonic stem (ES) cells derived from the ICM generate and shed microvesicles (MVs), a major class of extracellular vesicles (EVs), which influence trophoblast behaviour during the implantation process. The MV cargo proteins laminin and fibronectin interact with integrins along the surfaces of the trophoblasts, triggering the activation of two signalling kinases, JNK and FAK, and stimulating trophoblast migration. We further show that injecting MVs isolated from ES cells into blastocysts results in an increase in their implantation efficiency. Thus, these findings highlight a unique mechanism by which ES cells communicate with trophoblasts within the blastocyst to increase their ability to migrate into the uterus, thereby promoting one of the earliest and most important steps during pregnancy. It is unclear how embryonic stem cells (ESC) communicate with surrounding cells during implantation. Here, the authors show that microvesicles (MV) are shed from ESCs, activating integrin and JNK/FAK kinases in trophoblasts, stimulating migration in vitro, and injecting MVs enhances blastocyst implantation.