美国冷泉港实验室Anthony M. Zador、Xiaoyin Chen团队取得一项新突破。他们发现将条形码神经解剖学与空间转录谱相结合，可以识别与投射相关的基因。2021年5月10日出版的《自然-神经科学》发表了这项成果。
研究人员研发了BARseq2，其可在绘制投射图的同时通过原位测序检测多重基因表达。研究人员确定了小鼠运动皮层和听觉皮层29,933个细胞中钙粘连蛋白和细胞类型标记物的表达以及3,164个细胞的投射。在1,349个神经元中关联基因表达和投影揭示了跨两个皮层区域同源投射的共享钙粘连蛋白特征。这些钙粘连蛋白在转录组分类学的多个分支中富集。通过使多基因表达和预测与单个神经元中多靶点高通量相关联，BARseq2提供了揭示神经元回路分子特征的潜在途径。
据悉，功能电路是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，就需要在细胞水平利用高通量方法对同一细胞的基因表达和多靶点投射进行鉴别，然而当前的技术难以实现该要求。
附：英文原文
Title: Integrating barcoded neuroanatomy with spatial transcriptional profiling enables identification of gene correlates of projections
Author: Yu-Chi Sun, Xiaoyin Chen, Stephan Fischer, Shaina Lu, Huiqing Zhan, Jesse Gillis, Anthony M. Zador
Issue&Volume: 2021-05-10
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. Sun et al. present BARseq2, a high-throughput method combining in situ sequencing of endogenous mRNAs with barcode-based axonal projection mapping, and apply it to identify cadherins that correlate with similar projections in two cortical areas.
DOI: 10.1038/s41593-021-00842-4
Source: https://www.nature.com/articles/s41593-021-00842-4
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
