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Integrating barcoded neuroanatomy with spatial transcriptional profiling reveals cadherin correlates of projections shared across the cortex

View ORCID ProfileYu-Chi Sun, View ORCID ProfileXiaoyin Chen, View ORCID ProfileStephan Fischer, Shaina Lu, View ORCID ProfileJesse Gillis, View ORCID ProfileAnthony M. Zador
doi: https://doi.org/10.1101/2020.08.25.266460
Yu-Chi Sun
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Xiaoyin Chen
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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  • For correspondence: xichen@cshl.edu zador@cshl.edu
Stephan Fischer
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Shaina Lu
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Jesse Gillis
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Anthony M. Zador
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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  • For correspondence: xichen@cshl.edu zador@cshl.edu
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Abstract

Functional circuits consist of neurons with diverse axonal projections and gene expression. Understanding the molecular signature of projections requires high-throughput interrogation of both gene expression and projections to multiple targets in the same cells at cellular resolution, which is difficult to achieve using current technology. Here, we introduce BARseq2, a technique that simultaneously maps projections and detects multiplexed gene expression by in situ sequencing. We determined the expression of cadherins and cell-type markers in 29,933 cells, and the projections of 3,164 cells in both the mouse motor cortex and auditory cortex. Associating gene expression and projections in 1,349 neurons revealed shared cadherin signatures of homologous projections across the two cortical areas. These cadherins were enriched across multiple branches of the transcriptomic taxonomy. By correlating multi-gene expression and projections to many targets in single neurons with high throughput, BARseq2 provides a path to uncovering the molecular logic underlying neuronal circuits.

Competing Interest Statement

A.M.Z. is a founder and equity owner of Cajal Neuroscience and a member of its scientific advisory board.

Footnotes

  • https://data.mendeley.com/datasets/jnx89bmv4s/draft?a=4672e3ab-4097-4a1d-8e1e-3729b5b5e3b6

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 August 26, 2020.
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Integrating barcoded neuroanatomy with spatial transcriptional profiling reveals cadherin correlates of projections shared across the cortex
Yu-Chi Sun, Xiaoyin Chen, Stephan Fischer, Shaina Lu, Jesse Gillis, Anthony M. Zador
bioRxiv 2020.08.25.266460; doi: https://doi.org/10.1101/2020.08.25.266460
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Integrating barcoded neuroanatomy with spatial transcriptional profiling reveals cadherin correlates of projections shared across the cortex
Yu-Chi Sun, Xiaoyin Chen, Stephan Fischer, Shaina Lu, Jesse Gillis, Anthony M. Zador
bioRxiv 2020.08.25.266460; doi: https://doi.org/10.1101/2020.08.25.266460

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