Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Nat Neurosci. 2021 Jun;24(6):873-885. doi: 10.1038/s41593-021-00842-4. Epub 2021 May 10.
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.
功能回路由具有不同轴突投射和基因表达的神经元组成。要了解投射的分子特征，需要以细胞分辨率对同一细胞中的多个靶标进行基因表达和投射的高通量检测，这是当前技术难以实现的。在这里，我们介绍了 BARseq2，这是一种同时通过原位测序绘制投射并检测多路基因表达的技术。我们确定了在小鼠运动皮层和听觉皮层中的 29933 个细胞中的钙粘蛋白和细胞类型标志物的表达，以及 3164 个细胞的投射。在 1349 个神经元中关联基因表达和投射揭示了两个皮层区域同源投射的共享钙粘蛋白特征。这些钙粘蛋白在转录组分类学的多个分支中富集。通过高通量关联单个神经元中多个靶标上的多基因表达和投射，BARseq2 为揭示神经元回路背后的分子逻辑提供了一条潜在的途径。
