Suspended graphene oxide nanosheets maintain the self-renewal of mouse embryonic stem cells via down-regulating the expression of Vinculin

Suspended graphene oxide nanosheets maintain the self-renewal of mouse embryonic stem cells via down-regulating the expression of Vinculin
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悬浮氧化石墨烯纳米片通过下调Vinculin的表达维持小鼠胚胎干细胞的自我更新

DOI:
10.1016/j.biomaterials.2018.04.017
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发表时间:
2018-07-01
期刊:
影响因子:
14
通讯作者:
Zhu, Rongrong
Zhu, Rongrong
中科院分区:
工程技术1区
文献类型:
--
作者:
Jing, Guoxin;Wang, Zhaojie;Zhu, Rongrong

文献摘要

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氧化石墨烯(GO)具有良好的亲水性和生物相容性,在干细胞分化领域被广泛探索作为各种因子的载体。然而,其维持小鼠胚胎干细胞(mESCs)的干细胞性的功能和这一过程的潜在机制尚未被发现。本研究旨在探讨GO对mESCs的生物学功能,揭示GO参与的信号通路和关键基因。碱性磷酸酶活性检测、多能性基因定量和体内畸胎瘤形成证实GO纳米片可以维持mESC的自我更新能力而不影响其多能性。RNA-seq技术揭示了GO对mESCs的生物学作用与整合素信号通路的关系,并发现整合素是GO作用的关键基因。进一步的实验证实,表达下调的mESCs通过减少MEK 1的表达影响的命运。总之,该研究首次证明了mESCs具有维持自我更新的潜力,并阐明了这种功能的机制,使其在干细胞研究和再生医学中发挥新的作用。(C)2018爱思唯尔有限公司版权所有。
Graphene oxide (GO), with good hydrophilicity and biocompatibility, is widely explored as a carrier for various factors in the field of stem cell differentiation. However, its function of sustaining the stemness of mouse embryonic stem cells (mESCs) and the underlying mechanisms of this process remains undiscovered. Herein, we explored the biofunction of GO on mESCs and revealed the involved signaling pathways and key gene. The alkaline phosphatase activity detection, pluripotency genes quantification and the teratomas formation in vivo confirmed that GO nanosheets could sustain the self-renewal ability of mESCs instead of influencing its pluripotency. The underlying signaling pathways were uncovered by RNA-seq that integrin signaling pathway was involved in the biofunction of GO on mESCs and Vinculin turned to be a key gene for the effect of GO. Further experiments confirmed that the downregulation of Vinculin influenced the fate of mESCs through decreasing the expression of MEK1. Altogether, the study demonstrated for the first time that GOs hold the potential in sustaining the self-renewal of mESCs and clarified the mechanism of this function, which make it play a new role in stem cell research and regenerative medicine. (C) 2018 Elsevier Ltd. All rights reserved.