利用小分子将星形胶质细胞系转化为少突胶质细胞祖细胞并移植到多发性硬化症动物模型中

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2024-04-09 DOI:10.1007/s12031-024-02206-6
Mohsen Sharifi-Kelishadi, Leila Zare, Yaghoub Fathollahi, Mohammad Javan
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引用次数: 0

摘要

星形胶质细胞是中枢神经系统(CNS)中最常见的细胞,可通过特定的转录因子和一些化学物质转化为神经元和少突胶质祖细胞(OPC)。在本研究中,我们介绍了一种针对不同信号通路的鸡尾酒小分子,以促进星形胶质细胞向 OPCs 的转化。将星形胶质细胞转移到 OPC 培养基中,并在含有 CHIR99021、Forskolin、Repsox、LDN、VPA 和 Thiazovivin 的小分子鸡尾酒中暴露 5 天,然后在 OPC 培养基中再保存 10 天。达到 OPC 形态后,对诱导细胞进行 OPC 标记免疫荧光评估,同时检查是否缺乏星形胶质细胞标记。为了测试体内分化能力,将诱导的 OPC 移植到用铜试剂治疗 12 周的脱髓鞘小鼠大脑中。通过形态变化、PDGFR 和 O4 标记的表达以及向表达 MBP 的少突胶质细胞的终末分化,两种不同的星形胶质细胞系证明了使用这种小分子鸡尾酒向 OPCs 转化的潜力。将诱导的 OPCs 移植到脱髓鞘小鼠大脑后,它们能有效分化为成熟的少突胶质细胞。通过小分子鸡尾酒从星形胶质细胞中生成 OPCs,可能为多发性硬化症等以髓鞘脱失为特征的疾病中产生髓鞘修复所需的祖细胞提供了一条新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Conversion of Astrocyte Cell Lines to Oligodendrocyte Progenitor Cells Using Small Molecules and Transplantation to Animal Model of Multiple Sclerosis

Astrocytes, the most prevalent cells in the central nervous system (CNS), can be transformed into neurons and oligodendrocyte progenitor cells (OPCs) using specific transcription factors and some chemicals. In this study, we present a cocktail of small molecules that target different signaling pathways to promote astrocyte conversion to OPCs. Astrocytes were transferred to an OPC medium and exposed for five days to a small molecule cocktail containing CHIR99021, Forskolin, Repsox, LDN, VPA and Thiazovivin before being preserved in the OPC medium for an additional 10 days. Once reaching the OPC morphology, induced cells underwent immunocytofluorescence evaluation for OPC markers while checked for lacking the astrocyte markers. To test the in vivo differentiation capabilities, induced OPCs were transplanted into demyelinated mice brains treated with cuprizone over 12 weeks. Two distinct lines of astrocytes demonstrated the potential of conversion to OPCs using this small molecule cocktail as verified by morphological changes and the expression of PDGFR and O4 markers as well as the terminal differentiation to oligodendrocytes expressing MBP. Following transplantation into demyelinated mice brains, induced OPCs effectively differentiated into mature oligodendrocytes. The generation of OPCs from astrocytes via a small molecule cocktail may provide a new avenue for producing required progenitors necessary for myelin repair in diseases characterized by the loss of myelin such as multiple sclerosis.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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