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Spatial organization of the transcriptome in individual neurons

View ORCID ProfileGuiping Wang, View ORCID ProfileCheen-Euong Ang, View ORCID ProfileJean Fan, Andrew Wang, View ORCID ProfileJeffrey R. Moffitt, View ORCID ProfileXiaowei Zhuang
doi: https://doi.org/10.1101/2020.12.07.414060
Guiping Wang
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
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  • ORCID record for Guiping Wang
Cheen-Euong Ang
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
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Jean Fan
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
2Center for Computational Biology, Department of Biomedical Engineering, Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA
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Andrew Wang
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
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Jeffrey R. Moffitt
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
3Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
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Xiaowei Zhuang
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA
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  • For correspondence: zhuang@chemistry.harvard.edu
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Abstract

Neurons are highly polarized cells with complex neurite morphology. Spatial organization and local translation of RNAs in dendrites and axons play an important role in many neuronal functions. Here we performed super-resolution spatial profiling of RNAs inside individual neurons at the genome scale using multiplexed error-robust fluorescence in situ hybridization (MERFISH), and mapped the spatial organization of up to ∼4,200 RNA species (genes) across multiple length scales, ranging from sub-micrometer to millimeters. Our data generated a quantitative intra-neuronal atlas of RNAs with distinct transcriptome compositions in somata, dendrites, and axons, and revealed diverse sub-dendritic distribution patterns of RNAs. Moreover, our spatial analysis identified distinct groups of genes exhibiting specific spatial clustering of transcripts at the sub-micrometer scale that were dependent on protein synthesis and differentially dependent on synaptic activity. Overall, these data provide a rich resource for characterizing the subcellular organization of the transcriptome in neurons with high spatial resolution.

Competing Interest Statement

G.W. J.R.M. and X.Z. are inventors on patents applied for by Harvard University related to MERFISH. J.R.M. and X.Z. are a co-founders and consultants of Vizgen.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 07, 2020.
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Spatial organization of the transcriptome in individual neurons
Guiping Wang, Cheen-Euong Ang, Jean Fan, Andrew Wang, Jeffrey R. Moffitt, Xiaowei Zhuang
bioRxiv 2020.12.07.414060; doi: https://doi.org/10.1101/2020.12.07.414060
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Spatial organization of the transcriptome in individual neurons
Guiping Wang, Cheen-Euong Ang, Jean Fan, Andrew Wang, Jeffrey R. Moffitt, Xiaowei Zhuang
bioRxiv 2020.12.07.414060; doi: https://doi.org/10.1101/2020.12.07.414060

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