An activity-mediated transition in transcription in early postnatal neurons [10X]

The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function. RNA-seq from mouse neurons哺乳动物大脑的成熟进程发生于出生后，这一神经元发育阶段在自闭症、精神分裂症等神经系统疾病中常出现功能受损。然而，目前对于调控出生后大脑成熟的分子机制仍不甚明确。本研究通过纯化小鼠大脑发育各阶段的神经元亚群，鉴定出一套在成熟哺乳动物大脑中发挥作用的转录调控环路（transcriptional regulatory circuits）的出生后转换事件。研究表明，这一发育转变包含数百种细胞类型特异性神经元增强子（neuronal enhancers）在出生后阶段形成，这类增强子或可部分受神经元活动调控。一旦被选定激活，这些增强子将在整个成年期持续保持活性，这提示它们在生命早期的形成过程塑造了神经元身份，并调控成熟大脑的功能。本研究使用的转录组测序数据源自小鼠神经元的RNA测序（RNA-seq）。