阻遏元件-1 沉默转录因子 (REST) 是一种参与神经发育和神经保护的转录阻遏蛋白。 REST 与 REST 辅抑制子 CoREST1、CoREST2 或 CoREST3（分别由 RCOR1、RCOR2 和 RCOR3 编码）形成复合体。新出现的证据表明，CoREST 家族可以在不同发育阶段的各种神经细胞和神经胶质细胞类型中独立于 REST 靶向独特的基因。然而，关于 CoREST 家族在人类神经发育中的表达和功能的知识有限。为了解决这一差距，我们采用 2D 和 3D 人类多能干细胞 (hPSC) 模型来研究 REST 和 RCOR 基因表达水平。我们的研究揭示了谷氨酸能皮质和 GABA 能腹侧前脑神经元以及成熟的功能性 NGN2 诱导神经元中 RCOR3 表达显着增加。此外，简化的星形胶质细胞转分化方案导致分化后 RCOR2 表达显着下降。成熟神经元和大脑类器官中 REST 表达显着降低。总之，我们的研究结果首次深入了解了人类神经元和神经胶质细胞分化中 RCOR 基因的细胞类型特异性表达模式。具体来说，神经元中的 RCOR3 表达增加，而星形胶质细胞中的 RCOR2 水平降低。 hPSC 神经元和神经胶质分化过程中 REST 和 RCOR 基因的动态表达模式强调了 REST 和 CoREST 蛋白在调节人类这些细胞类型发育中所发挥的潜在独特作用。© 2024 作者。

Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor involved in neurodevelopment and neuroprotection. REST forms a complex with the REST corepressors, CoREST1, CoREST2, or CoREST3 (encoded by RCOR1, RCOR2, and RCOR3, respectively). Emerging evidence suggests that the CoREST family can target unique genes independently of REST, in various neural and glial cell types during different developmental stages. However, there is limited knowledge regarding the expression and function of the CoREST family in human neurodevelopment. To address this gap, we employed 2D and 3D human pluripotent stem cell (hPSC) models to investigate REST and RCOR gene expression levels. Our study revealed a significant increase in RCOR3 expression in glutamatergic cortical and GABAergic ventral forebrain neurons, as well as mature functional NGN2-induced neurons. Additionally, a simplified astrocyte transdifferentiation protocol resulted in a significant decrease in RCOR2 expression following differentiation. REST expression was notably reduced in mature neurons and cerebral organoids. In summary, our findings provide the first insights into the cell-type-specific expression patterns of RCOR genes in human neuronal and glial differentiation. Specifically, RCOR3 expression increases in neurons, while RCOR2 levels decrease in astrocytes. The dynamic expression patterns of REST and RCOR genes during hPSC neuronal and glial differentiation underscore the potential distinct roles played by REST and CoREST proteins in regulating the development of these cell types in humans.© 2024 The Authors.