The landscape of regulatory genes in brain-wide neuronal phenotypes of a vertebrate brain

eLife

Haifang Wang¹  Xiaoying Qiu¹  Xiaoyu Shen¹  Xinling Jia¹  Jie He¹  Jun Yan²  Jiulin Du²  Yufan Wang³  Shuguang Yu³  Hui Zhang³ 

[1] Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China;Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China;Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China;Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China;School of Future Technology, University of Chinese Academy of Sciences, Beijing, China;Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China;University of Chinese Academy of Sciences, Beijing, China;Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China;

关键词: regulatory gene;    effector gene;    neuronal phenotype;    zebrafish whole brain;    transcription factor;    RNA-binding protein;    Zebrafish;   

DOI  :  10.7554/eLife.68224

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive. We generated single-cell transcriptomes of ~67,000 region- and neurotransmitter/neuromodulator-identifiable cells from larval zebrafish brains. Hierarchical clustering based on effector gene profiles (‘terminal features’) distinguished major brain cell types. Sister clusters at hierarchical termini displayed similar terminal features. It was further verified by a population-level statistical method. Intriguingly, glutamatergic/GABAergic sister clusters mostly expressed distinct transcription factor (TF) profiles (‘convergent pattern’), whereas neuromodulator-type sister clusters predominantly expressed the same TF profiles (‘matched pattern’). Interestingly, glutamatergic/GABAergic clusters with similar TF profiles could also display different terminal features (‘divergent pattern’). It led us to identify a library of RNA-binding proteins that differentially marked divergent pair clusters, suggesting the post-transcriptional regulation of neuron diversification. Thus, our findings reveal multidimensional landscapes of transcriptional and post-transcriptional regulators in whole-brain neuronal phenotypes in the zebrafish brain.

【 授权许可】

CC BY