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来自生殖细胞的诱导神经元 于……中

Induced Neurons From Germ Cells in .

作者信息

Marchal Iris, Tursun Baris

机构信息

Berlin Institute for Medical Systems Biology, Berlin, Germany.

Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

出版信息

Front Neurosci. 2021 Dec 3;15:771687. doi: 10.3389/fnins.2021.771687. eCollection 2021.

Abstract

Cell fate conversion by the forced overexpression of transcription factors (TFs) is a process known as reprogramming. It leads to de-differentiation or differentiation of mature cells, which could then be used for regenerative medicine applications to replenish patients suffering from, e.g., neurodegenerative diseases, with healthy neurons. However, TF-induced reprogramming is often restricted due to cell fate safeguarding mechanisms, which require a better understanding to increase reprogramming efficiency and achieve higher fidelity. The germline of the nematode has been a powerful model to investigate the impediments of generating neurons from germ cells by reprogramming. A number of conserved factors have been identified that act as a barrier for TF-induced direct reprogramming of germ cells to neurons. In this review, we will first summarize our current knowledge regarding cell fate safeguarding mechanisms in the germline. Then, we will focus on the molecular mechanisms underlying neuronal induction from germ cells upon TF-mediated reprogramming. We will shortly discuss the specific characteristics that might make germ cells especially fit to change cellular fate and become neurons. For future perspectives, we will look at the potential of research in advancing our knowledge of the mechanisms that regulate cellular identity, and what implications this has for therapeutic approaches such as regenerative medicine.

摘要

通过强制过表达转录因子(TFs)来实现细胞命运转变是一个被称为重编程的过程。它会导致成熟细胞去分化或分化,进而可用于再生医学应用,为患有神经退行性疾病等的患者补充健康的神经元。然而,由于细胞命运保护机制,TF诱导的重编程常常受到限制,需要更好地理解这些机制以提高重编程效率并实现更高的保真度。线虫的生殖系一直是研究通过重编程从生殖细胞生成神经元的障碍的有力模型。已经鉴定出许多保守因子,它们是TF诱导生殖细胞直接重编程为神经元的障碍。在这篇综述中,我们首先将总结我们目前关于生殖系中细胞命运保护机制的知识。然后,我们将重点关注TF介导的重编程过程中生殖细胞向神经元诱导的分子机制。我们将简要讨论可能使生殖细胞特别适合改变细胞命运并成为神经元的特定特征。对于未来展望,我们将探讨线虫研究在推进我们对调节细胞身份的机制的认识方面的潜力,以及这对再生医学等治疗方法的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bd5/8678065/16cbde7de647/fnins-15-771687-g001.jpg

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