Department of Biology, New York University, New York, NY 10003, USA.
New York University Abu Dhabi, Saadiyat Island, Abu Dhabi, United Arab Emirates.
Cell. 2018 Jul 26;174(3):622-635.e13. doi: 10.1016/j.cell.2018.05.021. Epub 2018 Jun 18.
Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure.
转录因子调节神经元的分子、形态和生理特征，并产生其令人印象深刻的细胞类型多样性。为了深入了解转录因子调节细胞类型多样性的一般原则，我们使用大规模单细胞 RNA 测序来描述果蝇眼片中广泛的细胞多样性。我们对 55000 个单细胞进行了测序，并将其分配到 52 个簇中。我们使用 FACS 分选的单细胞类型和簇特异性基因的 RNA 测序验证和注释了许多簇。为了鉴定负责诱导特定终末分化特征的转录因子，我们生成了一个“随机森林”模型，结果表明 Apterous 和 Traffic-jam 转录因子分别在许多但不是所有的胆碱能和谷氨酸能神经元中起作用。事实上，相同的终末特征通常可以由不同的转录因子在不同的细胞类型中调节，这表明存在广泛的表型趋同。我们的数据提供了对复杂脑结构发育和功能特化的深入了解。
