Abstract
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 glutamatergic/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 transcriptional 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.
Data availability
Single cell RNA-seq data has been deposited on BIG (Genome Sequence Archive - CRA002361), which will be available upon the publication
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single-cell RNA sequencing of zebrafish whole brainGenome Sequence Archive, CRA002361.
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GSE105010_fall.inDrops.RData.gzNCBI gene expression GSE105010.
Article and author information
Author details
Funding
Shanghai Science and Technology Development Foundation (2018SHZDZX05)
- Jiulin Du
- Jun Yan
- Jie He
Chinese Academy of Sciences (XDB32000000)
- Jiulin Du
- Jun Yan
- Jie He
Shanghai Science and Technology Development Foundation (18JC1410100)
- Jiulin Du
- Jun Yan
- Jie He
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The landscape of regulatory genes in brain-wide neuronal phenotypes of a vertebrate brain
eLife 10:e68224.
https://doi.org/10.7554/eLife.68224
Further reading
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