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分化胶质细胞向去分化细胞的表型转换受叶酸受体 α 调控。

A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α.

机构信息

Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Institute of Advanced Sciences, Dartmouth, Massachusetts, USA.

出版信息

Stem Cells. 2019 Nov;37(11):1441-1454. doi: 10.1002/stem.3067. Epub 2019 Aug 14.

Abstract

In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA-FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction-1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor-1. Stem Cells 2019;37:1441-1454.

摘要

在之前的研究中,我们表明叶酸受体-α(FRα)易位到细胞核,在细胞核中作为转录因子,上调负责多能性的 Hes1、Oct4、Sox2 和 Klf4 基因。在这里,我们表明 FRα 的乙酰化和磷酸化有利于其在叶酸存在下的核易位,并可能导致分化的神经胶质细胞向去分化细胞的表型转变。使用 shRNA-FRα 介导的 FRα 敲低来确认 FRα 在去分化中的作用。神圣罗勒亲水性部分-1 处理不仅阻断了叶酸介导的神经胶质细胞去分化,而且还促进了去分化神经胶质细胞的再分化,这可能是通过减少核易位的~38 kDa FRα 及其与染色质组装因子-1 的后续相互作用来实现的。干细胞 2019;37:1441-1454.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de8b/6899875/8c8d2c8ad1a9/STEM-37-1441-g001.jpg

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