The specification of inhibitory neurons has been described for the mouse and human brain, and many studies have shown that pluripotent stem cells (PSCs) can be used to create interneurons in vitro. It is unclear whether in vitro methods to produce human interneurons generate all the subtypes found in brain, and how similar in vitro and in vivo interneurons are. We applied single-nuclei and single-cell transcriptomics to model interneuron development from human cortex and interneurons derived from PSCs. We provide a direct comparison of various in vitro interneuron derivation methods to determine the homogeneity achieved. We find that PSC-derived interneurons capture stages of development prior to mid-gestation, and represent a minority of potential subtypes found in brain. Comparison with those found in fetal or adult brain highlighted decreased expression of synapse-related genes. These analyses highlight the potential to tailor the method of generation to drive formation of particular subtypes.

抑制性神经元的规格已针对小鼠和人脑进行了描述，许多研究表明多能干细胞 (PSC) 可用于在体外创建中间神经元。目前尚不清楚产生人类中间神经元的体外方法是否会产生大脑中发现的所有亚型，以及体外和体内中间神经元的相似程度。我们应用单核和单细胞转录组学来模拟人类皮层的中间神经元发育和源自 PSC 的中间神经元。我们提供各种体外的直接比较中间神经元推导方法来确定所达到的同质性。我们发现 PSC 衍生的中间神经元捕获了妊娠中期之前的发育阶段，并代表了大脑中发现的少数潜在亚型。与在胎儿或成人大脑中发现的那些相比，突显了突触相关基因的表达减少。这些分析强调了调整生成方法以驱动特定亚型形成的潜力。