Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Neuron. 2019 Sep 4;103(5):785-801.e8. doi: 10.1016/j.neuron.2019.06.011. Epub 2019 Jul 11.
We performed RNA sequencing on 40,000 cells to create a high-resolution single-cell gene expression atlas of developing human cortex, providing the first single-cell characterization of previously uncharacterized cell types, including human subplate neurons, comparisons with bulk tissue, and systematic analyses of technical factors. These data permit deconvolution of regulatory networks connecting regulatory elements and transcriptional drivers to single-cell gene expression programs, significantly extending our understanding of human neurogenesis, cortical evolution, and the cellular basis of neuropsychiatric disease. We tie cell-cycle progression with early cell fate decisions during neurogenesis, demonstrating that differentiation occurs on a transcriptomic continuum; rather than only expressing a few transcription factors that drive cell fates, differentiating cells express broad, mixed cell-type transcriptomes before telophase. By mapping neuropsychiatric disease genes to cell types, we implicate dysregulation of specific cell types in ASD, ID, and epilepsy. We developed CoDEx, an online portal to facilitate data access and browsing.
我们对 40000 个细胞进行了 RNA 测序,构建了人类大脑皮层发育的高分辨率单细胞基因表达图谱,首次对以前未被表征的细胞类型进行了单细胞特征分析,包括人类基板神经元,与批量组织的比较,以及对技术因素的系统分析。这些数据允许对连接调控元件和转录驱动因子与单细胞基因表达程序的调控网络进行反卷积,极大地扩展了我们对人类神经发生、皮质进化和神经精神疾病细胞基础的理解。我们将细胞周期进程与神经发生过程中的早期细胞命运决定联系起来,证明分化是在转录组连续体上发生的;分化细胞在有丝分裂末期之前表达广泛的、混合的细胞类型转录组,而不是仅表达少数驱动细胞命运的转录因子。通过将神经精神疾病基因映射到细胞类型,我们暗示特定细胞类型的失调与 ASD、ID 和癫痫有关。我们开发了 CoDEx,这是一个在线门户,以方便数据访问和浏览。
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