小柯机器人

美国冷泉港实验室Anthony M. Zador等研究人员合作发现，全皮层原位测序揭示输入依赖性区域特征。相关论文于2024年4月24日在线发表在《自然》杂志上。

研究人员利用高通量原位测序技术BARseq，以细胞分辨率检测了1030万个细胞（包括九个小鼠前脑半球的4194658个皮层神经元）中104个细胞类型标记基因的表达。单个神经元基因表达的全新聚类显示了与之前单细胞RNA测序研究一致的转录组类型。转录组类型的组成可高度预测皮层区域的特征。此外，转录组类型组成相似的区域（研究人员将其定义为皮层模块）与高度连通的区域重叠，这表明转录组特征和连通性反映了相同的模块组织。

为了探索大脑皮层神经元的转录组特征如何依赖于发育，研究人员评估了新生小鼠双目摘除后的细胞类型分布。值得注意的是，双眼摘除导致视觉区域的细胞类型组成特征向同一模块内的相邻皮层区域转移，这表明外周输入使皮层模块内各区域的转录组特征更加明显。BARseq具有高通量、低成本和可重复性的特点，该研究证明了使用大规模原位测序揭示全脑分子结构并了解其发展的原理。

研究人员表示，大脑皮层由具有不同基因表达的神经元类型组成，这些神经元类型被组织成专门的皮层区域。这些区域各具特色的细胞结构、连接性和神经元活动，被连接成模块化网络。然而，这些空间组织是否反映在神经元转录组特征中，以及这些特征是如何在发育过程中建立起来的，目前仍不清楚。

附：英文原文

Title: Whole-cortex in situ sequencing reveals input-dependent area identity

Author: Chen, Xiaoyin, Fischer, Stephan, Rue, Mara C. P., Zhang, Aixin, Mukherjee, Didhiti, Kanold, Patrick O., Gillis, Jesse, Zador, Anthony M.

Issue&Volume: 2024-04-24

Abstract: The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each with characteristic cytoarchitecture1,2, connectivity3,4 and neuronal activity5,6, are wired into modular networks3,4,7. However, it remains unclear whether these spatial organizations are reflected in neuronal transcriptomic signatures and how such signatures are established in development. Here we used BARseq, a high-throughput in situ sequencing technique, to interrogate the expression of 104 cell-type marker genes in 10.3 million cells, including 4,194,658 cortical neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering of gene expression in single neurons revealed transcriptomic types consistent with previous single-cell RNA sequencing studies8,9. The composition of transcriptomic types is highly predictive of cortical area identity. Moreover, areas with similar compositions of transcriptomic types, which we defined as cortical modules, overlap with areas that are highly connected, suggesting that the same modular organization is reflected in both transcriptomic signatures and connectivity. To explore how the transcriptomic profiles of cortical neurons depend on development, we assessed cell-type distributions after neonatal binocular enucleation. Notably, binocular enucleation caused the shifting of the cell-type compositional profiles of visual areas towards neighbouring cortical areas within the same module, suggesting that peripheral inputs sharpen the distinct transcriptomic identities of areas within cortical modules. Enabled by the high throughput, low cost and reproducibility of BARseq, our study provides a proof of principle for the use of large-scale in situ sequencing to both reveal brain-wide molecular architecture and understand its development. BARseq interrogates the expression of 104 cell-type marker genes in 10.3 million cells over nine mouse forebrain hemispheres to reveal the role of peripheral inputs on cortical area development.

DOI: 10.1038/s41586-024-07221-6

Source: https://www.nature.com/articles/s41586-024-07221-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html