Integrating barcoded neuroanatomy with spatial transcriptional profiling enables identification of gene correlates of projections

Sun, Yu-Chi, Chen, Xiaoyin, Fischer, Stephan, Lu, Shaina, Zhan, Huiqing, Gillis, Jesse, Zador, Anthony M (May 2021) Integrating barcoded neuroanatomy with spatial transcriptional profiling enables identification of gene correlates of projections. Nature Neuroscience. ISSN 1097-6256

URL: https://www.ncbi.nlm.nih.gov/pubmed/33972801

DOI: 10.1038/s41593-021-00842-4

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 multigene expression and projections to many targets in single neurons with high throughput, BARseq2 provides a potential path to uncovering the molecular logic underlying neuronal circuits.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription organism description > animal organs, tissues, organelles, cell types and functions > tissues types and functions > auditory cortex bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cadherin bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression organism description > animal > mammal organs, tissues, organelles, cell types and functions > tissues types and functions > motor cortex organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Sun, Yu-Chi Chen, Xiaoyin Fischer, Stephan Zhan, Huiqing Gillis, Jesse Zador, Anthony M. Lu, Shaina
Communities:	CSHL labs > Gillis Lab CSHL labs > Zador lab School of Biological Sciences > Publications CSHL Cancer Center Program CSHL Cancer Center Program > Cellular Communication in Cancer Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	10 May 2021
Date Deposited:	12 May 2021 13:17
Last Modified:	13 Feb 2024 19:22
PMCID:	PMC8178227
URI:	https://repository.cshl.edu/id/eprint/40088

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