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直接神经元重编程揭示已知转录因子的未知功能。

Direct Neuronal Reprogramming Reveals Unknown Functions for Known Transcription Factors.

作者信息

Colasante Gaia, Rubio Alicia, Massimino Luca, Broccoli Vania

机构信息

Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.

CNR Institute of Neuroscience, Milan, Italy.

出版信息

Front Neurosci. 2019 Mar 26;13:283. doi: 10.3389/fnins.2019.00283. eCollection 2019.

Abstract

In recent years, the need to derive sources of specialized cell types to be employed for cell replacement therapies and modeling studies has triggered a fast acceleration of novel cell reprogramming methods. In particular, in neuroscience, a number of protocols for the efficient differentiation of somatic or pluripotent stem cells have been established to obtain a renewable source of different neuronal cell types. Alternatively, several neuronal populations have been generated through direct reprogramming/transdifferentiation, which concerns the conversion of fully differentiated somatic cells into induced neurons. This is achieved through the forced expression of selected transcription factors (TFs) in the donor cell population. The reprogramming cocktail is chosen after an accurate screening process involving lists of TFs enriched into desired cell lineages. In some instances, this type of studies has revealed the crucial role of TFs whose function in the differentiation of a given specific cell type had been neglected or underestimated. Herein, we will speculate on how the studies have served to better understand physiological mechanisms of neuronal development .

摘要

近年来,为细胞替代疗法和模型研究获取专用细胞类型来源的需求,促使新型细胞重编程方法迅速加速发展。特别是在神经科学领域,已经建立了许多用于有效分化体细胞或多能干细胞的方案,以获得不同神经元细胞类型的可再生来源。另外,通过直接重编程/转分化也产生了几种神经元群体,这涉及将完全分化的体细胞转化为诱导神经元。这是通过在供体细胞群体中强制表达选定的转录因子(TFs)来实现的。重编程混合物是在经过精确筛选过程后选择的,该过程涉及富含所需细胞谱系的TFs列表。在某些情况下,这类研究揭示了一些转录因子的关键作用,而这些转录因子在特定细胞类型分化中的功能此前被忽视或低估了。在此,我们将推测这些研究如何有助于更好地理解神经元发育的生理机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/389b/6445133/fb86f565d6b2/fnins-13-00283-g001.jpg

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