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EID3 在人脐带间充质干细胞向 NPC 样细胞的转分化过程中直接与 DNMT3A 结合。

EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells.

机构信息

Bayi Brain Hospital, General Hospital of PLA Army, Southern Medical University, Beijing 100700, P. R. China.

Stem Cell Research Center, Neurosurgery Institute of Beijing Military Region, Beijing 100700, P. R. China.

出版信息

Sci Rep. 2017 Jan 11;7:40463. doi: 10.1038/srep40463.

Abstract

There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.

摘要

最近,人们对人脐带间充质干细胞(UMSC)的可塑性及其在治疗神经紊乱方面的潜力产生了浓厚的兴趣。在这项研究中,UMSC 被诱导分化为神经干细胞样细胞(uNSCL),这些细胞在神经球样结构中生长并表达高水平的神经干细胞标志物。本研究通过筛选与表观遗传学相关的基因,评估 E1A 样分化抑制因子 3(EID3),一种 p300 抑制剂,以及 DNA 甲基转移酶 3A(DNMT3A)在 UMSC 体外向 uNSCL 分化过程中的关系。在 UMSC 向 uNSCL 分化之前,检测到 EID3 水平较高,DNMT3A 水平较低;分化后,EID3 水平降低,DNMT3A 水平升高。目前的工作表明,EID3 和 DNMT3A 在细胞核中共定位,并且 EID3 在 uNSCL 中与 DNMT3A 直接相互作用。综上所述,这些结果表明,在 UMSC 向 uNSCL 分化过程中,DNMT3A 可能被 EID3 直接调控。这些发现表明,EID3,一种 p300 乙酰转移酶抑制剂,可以直接影响 DNMT3A,这种酶具有双重甲基化和去甲基化能力。这些研究可能有助于理解 DNMT3A 的复杂调控模式,DNMT3A 是甲基转移酶家族中独特的一员。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a88/5225425/6543e60e6bca/srep40463-f1.jpg

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