RT Journal Article SR Electronic T1 Integrating barcoded neuroanatomy with spatial transcriptional profiling reveals cadherin correlates of projections shared across the cortex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.25.266460 DO 10.1101/2020.08.25.266460 A1 Yu-Chi Sun A1 Xiaoyin Chen A1 Stephan Fischer A1 Shaina Lu A1 Jesse Gillis A1 Anthony M. Zador YR 2020 UL http://biorxiv.org/content/early/2020/08/26/2020.08.25.266460.abstract AB 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 StatementA.M.Z. is a founder and equity owner of Cajal Neuroscience and a member of its scientific advisory board.