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高通量分析树突和轴突分支揭示了神经解剖学的转录组相关性。

High-throughput analysis of dendrite and axonal arbors reveals transcriptomic correlates of neuroanatomy.

机构信息

Allen Institute, Seattle, WA, USA.

California Institute of Technology, Pasadena, CA, USA.

出版信息

Nat Commun. 2024 Jul 27;15(1):6337. doi: 10.1038/s41467-024-50728-9.

Abstract

Neuronal anatomy is central to the organization and function of brain cell types. However, anatomical variability within apparently homogeneous populations of cells can obscure such insights. Here, we report large-scale automation of neuronal morphology reconstruction and analysis on a dataset of 813 inhibitory neurons characterized using the Patch-seq method, which enables measurement of multiple properties from individual neurons, including local morphology and transcriptional signature. We demonstrate that these automated reconstructions can be used in the same manner as manual reconstructions to understand the relationship between some, but not all, cellular properties used to define cell types. We uncover gene expression correlates of laminar innervation on multiple transcriptomically defined neuronal subclasses and types. In particular, our results reveal correlates of the variability in Layer 1 (L1) axonal innervation in a transcriptomically defined subpopulation of Martinotti cells in the adult mouse neocortex.

摘要

神经元解剖结构是大脑细胞类型的组织和功能的核心。然而,在明显同质的细胞群体中,解剖结构的可变性可能会掩盖这些见解。在这里,我们报告了在使用 Patch-seq 方法对 813 个抑制性神经元进行特征描述的数据集上进行大规模神经元形态重建和分析的自动化,该方法可以测量单个神经元的多个特性,包括局部形态和转录特征。我们证明,这些自动重建可以与手动重建一样用于理解某些细胞特性,但不是所有细胞特性之间的关系,这些特性用于定义细胞类型。我们在多个转录定义的神经元亚类和类型上揭示了与层状神经支配相关的基因表达相关性。特别是,我们的结果揭示了成年小鼠新皮层中 Martinotti 细胞转录定义亚群中 L1(L1)轴突神经支配变异性的相关因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab6c/11283452/db84bf25758c/41467_2024_50728_Fig1_HTML.jpg

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