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Morphological diversity of single neurons in molecularly defined cell types

机译：分子定义细胞类型中单个神经元的形态样

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摘要

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types~(1,2), yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
机译：树突和轴突形态反映了神经元的输入和输出，是神经元类型的定义特征〜（1,2），但我们对其多样性的了解仍然有限。在这里，为了系统地检查完全的单神经元形态，我们建立了包含稀疏标记，全脑成像，重建，注册和分析的管道。我们完全重建了1,741名神经元，从皮质，克劳斯，丘脑，纹状体和小鼠中的其他脑区。我们鉴定了11个主要投影神经元类型，具有不同的形态学特征和相应的转录组特征。在这些主要类型中的每种类型中发现了广泛的突出分集，其中一些类型被聚集成更精致的亚型。这种多样性遵循一组可概括的原理，该原理管辖不同水平的远程轴突投影，包括分子对应，发散或会聚投影，轴路终止模式，区域特异性，地形和个体细胞变异性。尽管在主要投影型的水平下，具有转录组曲线的明显一致性，但细粒的形态多样性往往不会易于与来自无监督聚类的转录组亚型相关，突出了对单细胞跨模型研究的需求。总体而言，我们的研究表明，对于细胞型分类的完全单细胞解剖学的定量描述至关重要，因为单细胞形态多样性揭示了不同细胞类型和其各个成员可能有助于配置和功能的多种方式他们各自的电路。

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  • 来源
    《Nature》 |2021年第7879期|174-181|共8页
  • 作者

    Hanchuan Peng; Peng Xie; Lijuan Liu; Xiuli Kuang; Yimin Wang; Lei Qu; Hui Gong; Shengdian Jiang; Anan Li; Zongcai Ruan; Liya Ding; Zizhen Yao; Chao Chen; Mengya Chen; Tanya L Daigle; Rachel Dalley; Zhangcan Ding; Yanjun Duan; Aaron Feiner; Ping He; Chris Hill; Karla E Hirokawa; Guodong Hong; Lei Huang; Sara Kebede; Hsien-Chi Kuo; Rachael Larsen; Phil Lesnar; Longfei Li; Qi Li; Xiangning Li; Yaoyao Li; Yuanyuan Li; An Liu; Donghuan Lu; Stephanie Mok; Lydia Ng; Thuc Nghi Nguyen; Qiang Ouyang; Jintao Pan; Elise Shen; Yuanyuan Song; Susan M Sunkin; Bosiljka Tasic; Matthew B Veldman; Wayne Wakeman; Wan Wan; Peng Wang; Quanxin Wang; Tao Wang; Yaping Wang; Feng Xiong; Wei Xiong; Wenjie Xu; Min Ye; Lulu Yin; Yang Yu; Jia Yuan; Jing Yuan; Zhixi Yun; Shaoqun Zeng; Shichen Zhang; Sujun Zhao; Zijun Zhao; Zhi Zhou; Z Josh Huang; Luke Esposito; Michael J Hawrylycz; Staci A Sorensen; X William Yang; Yefeng Zheng; Zhongze Gu; Wei Xie; Christof Koch; Qingming Luo; Julie A Harris; Yun Wang; Hongkui Zeng;

  • 作者单位

    Allen Institute for Brain Science|SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Ministry of Education Key Laboratory of Developmental Genes and Human Disease School of Life Science and Technology Southeast University;

    School of Optometry and Ophthalmology Wenzhou Medical University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|School of Computer Engineering and Science Shanghai University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Key Laboratory of Intelligent Computation and Signal Processing Ministry of Education Anhui University;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology|HUST-Suzhou Institute for Brainsmatics JITRI Institute for Brainsmatics;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology|HUST-Suzhou Institute for Brainsmatics JITRI Institute for Brainsmatics;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    School of Optometry and Ophthalmology Wenzhou Medical University;

    School of Computer Engineering and Science Shanghai University;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    School of Computer Engineering and Science Shanghai University;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science|Cajal Neuroscience;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Ministry of Education Key Laboratory of Developmental Genes and Human Disease School of Life Science and Technology Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Key Laboratory of Intelligent Computation and Signal Processing Ministry of Education Anhui University;

    School of Computer Engineering and Science Shanghai University;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology|HUST-Suzhou Institute for Brainsmatics JITRI Institute for Brainsmatics;

    School of Optometry and Ophthalmology Wenzhou Medical University;

    Key Laboratory of Intelligent Computation and Signal Processing Ministry of Education Anhui University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Ministry of Education Key Laboratory of Developmental Genes and Human Disease School of Life Science and Technology Southeast University;

    Tencent Jarvis Lab;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science|Cajal Neuroscience;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Center for Neurobehavioral Genetics Jane and Terry Semel Institute for Neuroscience and Human Behavior Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine University of California;

    Allen Institute for Brain Science;

    Key Laboratory of Intelligent Computation and Signal Processing Ministry of Education Anhui University;

    School of Computer Engineering and Science Shanghai University;

    Allen Institute for Brain Science;

    Key Laboratory of Intelligent Computation and Signal Processing Ministry of Education Anhui University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    School of Optometry and Ophthalmology Wenzhou Medical University;

    Allen Institute for Brain Science;

    School of Optometry and Ophthalmology Wenzhou Medical University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Ministry of Education Key Laboratory of Developmental Genes and Human Disease School of Life Science and Technology Southeast University;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology|HUST-Suzhou Institute for Brainsmatics JITRI Institute for Brainsmatics;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    Allen Institute for Brain Science;

    Cold Spring Harbor Laboratory|Department of Neurobiology Duke University School of Medicine;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

    Center for Neurobehavioral Genetics Jane and Terry Semel Institute for Neuroscience and Human Behavior Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine University of California;

    Tencent Jarvis Lab;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University;

    SEU-ALLEN Joint Center Institute for Brain and Intelligence Southeast University|Ministry of Education Key Laboratory of Developmental Genes and Human Disease School of Life Science and Technology Southeast University;

    Allen Institute for Brain Science;

    Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology|School of Biomedical Engineering Hainan University;

    Allen Institute for Brain Science|Cajal Neuroscience;

    Allen Institute for Brain Science;

    Allen Institute for Brain Science;

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