Studying human somatic cell-to-neuron conversion using primary brain-derived cells as starting cell source is hampered by limitations and variations in human biopsy material. Thus, delineating the molecular variables that allow changing the identity of somatic cells, permit adoption of neuronal phenotypes, and foster maturation of induced neurons (iNs) is challenging. Based on our previous results that pericytes derived from the adult human cerebral cortex can be directly converted into iNs (Karow et al., 2018; Karow et al., 2012), we here introduce human induced pluripotent stem cell (hiPSC)-derived pericytes (hiPSC-pericytes) as a versatile and more uniform tool to study the pericyte-to-neuron conversion process. This strategy enables us to derive scalable cell numbers and allows for engineering of the starting cell population such as introducing reporter tools before differentiation into hiPSC-pericytes and subsequent iN conversion. Harvesting the potential of this approach, we established hiPSC-derived human-human neuronal cocultures that not only allow for independent manipulation of each coculture partner but also resulted in morphologically more mature iNs. In summary, we exploit hiPSC-based methods to facilitate the analysis of human somatic cell-to-neuron conversion.

中文翻译：

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人类诱导多能干细胞衍生的周细胞作为可扩展和可编辑的来源来研究直接谱系重编程为诱导神经元。

使用原代脑源细胞作为起始细胞来源研究人类体细胞到神经元的转化受到人类活检材料的限制和变化的阻碍。因此，描绘允许改变体细胞身份、允许采用神经元表型并促进诱导神经元 (iN) 成熟的分子变量是具有挑战性的。基于我们之前的研究结果，来自成人大脑皮层的周细胞可以直接转化为 iNs (Karow et al., 2018; Karow et al., 2012)，我们在此介绍人类诱导多能干细胞 (hiPSC) 衍生的周细胞（hiPSC-周细胞）作为研究周细胞到神经元转换过程的通用且更统一的工具。该策略使我们能够获得可扩展的细胞数量，并允许对起始细胞群进行工程设计，例如在分化为 hiPSC-周细胞和随后的 iN 转换之前引入报告工具。为了发挥这种方法的潜力，我们建立了 hiPSC 衍生的人-人神经元共培养物，不仅允许独立操作每个共培养伙伴，而且还产生了形态上更成熟的 iN。总之，我们利用基于 hiPSC 的方法来促进人类体细胞到神经元转化的分析。