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Transcription Factor-Based Strategies to Generate Neural Cell Types from Human Pluripotent Stem Cells
Cellular Reprogramming ( IF 1.2 ) Pub Date : 2021-08-13 , DOI: 10.1089/cell.2021.0045
Isaac Canals 1, 2, 3 , Ella Quist 1, 2, 3 , Henrik Ahlenius 1, 2, 3
Affiliation  

In the last years, the use of pluripotent stem cells in studies of human biology has grown exponentially. These cells represent an infinite source for differentiation into several human cell types facilitating the investigation on biological processes, functionality of cells, or diseases mechanisms in relevant human models. In the neurobiology field, pluripotent stem cells have been extensively used to generate the main neuronal and glial cells of the brain. Traditionally, protocols following developmental cues have been applied to pluripotent stem cells to drive differentiation toward different cell lineages; however, these protocols give rise to populations with mixed identities. Interestingly, new protocols applying overexpression of lineage-specific transcription factors (TFs) have emerged and facilitated the generation of highly pure populations of specific subtypes of neurons and glial cells in an easy, reproducible, and rapid manner. In this study, we review protocols based on this strategy to generate excitatory, inhibitory, dopaminergic, and motor neurons as well as astrocytes, oligodendrocytes, and microglia. In addition, we will discuss the main applications for cells generated with these protocols, including disease modeling, drug screening, and mechanistic studies. Finally, we will discuss the advantages and disadvantages of TF-based protocols and present our view of the future in this field.

中文翻译:

从人类多能干细胞生成神经细胞类型的基于转录因子的策略

在过去几年中,多能干细胞在人类生物学研究中的应用呈指数级增长。这些细胞代表了一种无限的来源,可分化为几种人类细胞类型,从而有助于研究相关人体模型中的生物过程、细胞功能或疾病机制。在神经生物学领域,多能干细胞已被广泛用于生成大脑的主要神经元和神经胶质细胞。传统上,遵循发育线索的方案已应用于多能干细胞,以推动向不同细胞谱系的分化。然而,这些协议产生了具有混合身份的人群。有趣的是,已经出现了应用谱系特异性转录因子 (TF) 过表达的新方案,并促进了以简单、可重复和快速的方式生成高纯度的特定亚型神经元和神经胶质细胞群。在本研究中,我们回顾了基于此策略生成兴奋性、抑制性、多巴胺能和运动神经元以及星形胶质细胞、少突胶质细胞和小胶质细胞的协议。此外,我们将讨论使用这些协议生成的细胞的主要应用,包括疾病建模、药物筛选和机制研究。最后,我们将讨论基于 TF 的协议的优缺点,并提出我们对该领域未来的看法。我们审查了基于该策略生成兴奋性、抑制性、多巴胺能和运动神经元以及星形胶质细胞、少突胶质细胞和小胶质细胞的协议。此外,我们将讨论使用这些协议生成的细胞的主要应用,包括疾病建模、药物筛选和机制研究。最后,我们将讨论基于 TF 的协议的优缺点,并提出我们对该领域未来的看法。我们审查了基于该策略生成兴奋性、抑制性、多巴胺能和运动神经元以及星形胶质细胞、少突胶质细胞和小胶质细胞的协议。此外,我们将讨论使用这些协议生成的细胞的主要应用,包括疾病建模、药物筛选和机制研究。最后,我们将讨论基于 TF 的协议的优缺点,并提出我们对该领域未来的看法。
更新日期:2021-08-15
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