VIB Center for Brain & Disease Research, KU Leuven, Leuven 3000, Belgium; Department of Human Genetics KU Leuven, Leuven 3000, Belgium.
VIB Center for Brain & Disease Research, KU Leuven, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven, Leuven 3000, Belgium.
Cell. 2018 Aug 9;174(4):982-998.e20. doi: 10.1016/j.cell.2018.05.057. Epub 2018 Jun 18.
The diversity of cell types and regulatory states in the brain, and how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas of the entire adult Drosophila melanogaster brain sampled across its lifespan. Cell clustering identified 87 initial cell clusters that are further subclustered and validated by targeted cell-sorting. Our data show high granularity and identify a wide range of cell types. Gene network analyses using SCENIC revealed regulatory heterogeneity linked to energy consumption. During aging, RNA content declines exponentially without affecting neuronal identity in old brains. This single-cell brain atlas covers nearly all cells in the normal brain and provides the tools to study cellular diversity alongside other Drosophila and mammalian single-cell datasets in our unique single-cell analysis platform: SCope (http://scope.aertslab.org). These results, together with SCope, allow comprehensive exploration of all transcriptional states of an entire aging brain.
大脑中的细胞类型和调控状态的多样性,以及这些在衰老过程中如何变化,在很大程度上仍然未知。我们呈现了一个整个成年果蝇大脑在其整个生命周期中取样的单细胞转录组图谱。细胞聚类确定了 87 个初始细胞簇,这些细胞簇通过靶向细胞分选进一步细分和验证。我们的数据显示了很高的粒度,并鉴定了广泛的细胞类型。使用 SCENIC 的基因网络分析揭示了与能量消耗相关的调控异质性。在衰老过程中,RNA 含量呈指数级下降,而不会影响老年大脑中的神经元身份。这个单细胞大脑图谱几乎涵盖了正常大脑中的所有细胞,并提供了工具,可在我们独特的单细胞分析平台 SCope(http://scope.aertslab.org)中与其他果蝇和哺乳动物单细胞数据集一起研究细胞多样性。这些结果与 SCope 一起,允许对整个衰老大脑的所有转录状态进行全面探索。