Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK.
Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK.
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DOI：
10.1016/j.devcel.2020.11.017
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发表时间：
2021-02-08
影响因子：
11.8
通讯作者：
Antonyak MA
中科院分区：
文献类型：
--
作者：
Hur YH;Feng S;Wilson KF;Cerione RA;Antonyak MA
囊胚期胚胎中的上胚层细胞得到必要的调控信号，以保持多能性，直到它们被刺激进行分化，最终形成整个有机体，这一点至关重要。在这里，我们展示了胚胎干细胞(ESCs)在体外相当于上皮细胞，暴露于ESC来源的细胞外小泡(EVS)有助于保持其干细胞特性，即使在否则会诱导分化的培养条件下也是如此。EV处理的ESCs继续表达干细胞基因，保留了它们的多能性和产生嵌合体小鼠的能力。这些效应是由结合在EVS表面的纤维连接蛋白触发的，使它们能够与ESC相关的整合素相互作用，并比单独使用纤维连接蛋白更有效地激活FAK。总体而言，这些发现突显了一种潜在的调控机制，即外胚层细胞通过其脱落的EVS在胚泡内创造环境，防止其过早分化并保持其多能性状态。实际上，所有的细胞都会形成并释放多种不同类别的胞外小泡，包括微泡和外切体，以便与周围环境沟通。在这里，Hur等人。表明胚胎干细胞利用这种形式的细胞间通讯作为一种机制，帮助维持干细胞利基的多能性。
It is critical that epiblast cells within blastocyst-stage embryos receive the necessary regulatory cues to remain pluripotent until the appropriate time when they are stimulated to undergo differentiation, ultimately to give rise to an entire organism. Here, we show that exposure of embryonic stem cells (ESCs), which are the in vitro equivalents of epiblasts, to ESC-derived extracellular vesicles (EVs) helps to maintain their stem cell properties even under culture conditions that would otherwise induce differentiation. EV-treated ESCs continued to express stemness genes, preserving their pluripotency and ability to generate chimeric mice. These effects were triggered by fibronectin bound to the surfaces of EVs, enabling them to interact with ESC-associated integrins and activate FAK more effectively than fibronectin alone. Overall, these findings highlight a potential regulatory mechanism whereby epiblast cells, via their shed EVs, create an environment within the blastocyst that prevents their premature differentiation and maintains their pluripotent state. Virtually all cells form and release multiple distinct classes of extracellular vesicles, including microvesicles and exosomes, to communicate with their surroundings. Here, Hur et al. show that embryonic stem cells use this form of intercellular communication as a mechanism to help maintain the pluripotency of the stem cell niche.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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