Abstract：
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.
摘要：
使用原发性脑源性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的分子变量，允许采用神经元表型，诱导神经元(iNs)的培养成熟是具有挑战性的。根据我们先前的结果，来自成年人大脑皮层的周细胞可以直接转化为iN（Karow等人。,2018；Karow等人。,2012),我们在这里介绍人类诱导多能干细胞（hiPSC）衍生的周细胞（hiPSC-pericytes）作为研究周细胞向神经元转化过程的通用和更统一的工具。该策略使我们能够获得可缩放的细胞数量，并允许对起始细胞群进行工程改造，例如在分化为hiPSC周细胞和随后的iN转化之前引入报告工具。收获这种方法的潜力，我们建立了源自hiPSC的人-人神经元共培养物,这种共培养物不仅允许对每个共培养伴侣进行独立操作,而且导致形态学上更成熟的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换的分析。
