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Morphological diversity of single neurons in molecularly defined cell types
Nature ( IF 64.8 ) Pub Date : 2021-10-06 , DOI: 10.1038/s41586-021-03941-1
Hanchuan Peng 1, 2 , Peng Xie 2 , Lijuan Liu 2, 3 , Xiuli Kuang 4 , Yimin Wang 2, 5 , Lei Qu 2, 6 , Hui Gong 7, 8 , Shengdian Jiang 2 , Anan Li 7, 8 , Zongcai Ruan 2 , Liya Ding 2 , Zizhen Yao 1 , Chao Chen 4 , Mengya Chen 5 , Tanya L Daigle 1 , Rachel Dalley 1 , Zhangcan Ding 2 , Yanjun Duan 2 , Aaron Feiner 1 , Ping He 5 , Chris Hill 1 , Karla E Hirokawa 1, 9 , Guodong Hong 2, 3 , Lei Huang 2 , Sara Kebede 1 , Hsien-Chi Kuo 1 , Rachael Larsen 1 , Phil Lesnar 1 , Longfei Li 6 , Qi Li 5 , Xiangning Li 7, 8 , Yaoyao Li 4 , Yuanyuan Li 6 , An Liu 2, 3 , Donghuan Lu 10 , Stephanie Mok 1 , Lydia Ng 1 , Thuc Nghi Nguyen 1, 9 , Qiang Ouyang 2 , Jintao Pan 2 , Elise Shen 1 , Yuanyuan Song 2 , Susan M Sunkin 1 , Bosiljka Tasic 1 , Matthew B Veldman 11 , Wayne Wakeman 1 , Wan Wan 6 , Peng Wang 5 , Quanxin Wang 1 , Tao Wang 6 , Yaping Wang 2 , Feng Xiong 2 , Wei Xiong 4 , Wenjie Xu 1 , Min Ye 4 , Lulu Yin 2 , Yang Yu 1 , Jia Yuan 2, 3 , Jing Yuan 7, 8 , Zhixi Yun 2 , Shaoqun Zeng 7 , Shichen Zhang 2 , Sujun Zhao 2 , Zijun Zhao 2 , Zhi Zhou 1 , Z Josh Huang 12, 13 , Luke Esposito 1 , Michael J Hawrylycz 1 , Staci A Sorensen 1 , X William Yang 11 , Yefeng Zheng 10 , Zhongze Gu 2 , Wei Xie 2, 3 , Christof Koch 1 , Qingming Luo 7, 14 , Julie A Harris 1, 9 , Yun Wang 1 , Hongkui Zeng 1
Affiliation  

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, 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.



中文翻译:

分子定义的细胞类型中单个神经元的形态多样性

树突状和轴突形态反映了神经元的输入和输出,是神经元类型1,2的定义特征,但我们对其多样性的了解仍然有限。在这里,为了在全脑范围内系统地检查完整的单神经元形态,我们建立了一个包含稀疏标记、全脑成像、重建、注册和分析的管道。我们从小鼠的皮质、屏状核、丘脑、纹状体和其他大脑区域完全重建了 1,741 个神经元。我们确定了 11 种主要的投射神经元类型,它们具有不同的形态特征和相应的转录组学特征。在这些主要类型中的每一个中都发现了广泛的投影多样性,在此基础上,一些类型被聚类成更精细的子类型。这种多样性遵循一组可概括的原则,这些原则控制着不同水平的长程轴突投射,包括分子对应、发散或会聚投射,轴突终止模式、区域特异性、地形图和单个细胞变异性。尽管在主要投影类型的水平上与转录组学特征明显一致,但细粒度的形态多样性通常不容易与源自无监督聚类的转录组学亚型相关联,这突出了单细胞交叉模态研究的必要性。总的来说,我们的研究证明了在细胞类型分类中对完整的单细胞解剖结构进行定量描述的关键需求,因为单细胞形态多样性揭示了不同细胞类型及其个体成员可能对结构和功能做出贡献的多种方式他们各自的电路。尽管在主要投影类型的水平上与转录组学特征明显一致,但细粒度的形态多样性通常不容易与源自无监督聚类的转录组学亚型相关联,这突出了单细胞交叉模态研究的必要性。总的来说,我们的研究证明了在细胞类型分类中对完整的单细胞解剖结构进行定量描述的关键需求,因为单细胞形态多样性揭示了不同细胞类型及其个体成员可能对结构和功能做出贡献的多种方式他们各自的电路。尽管在主要投影类型的水平上与转录组学特征明显一致,但细粒度的形态多样性通常不容易与源自无监督聚类的转录组学亚型相关联,这突出了单细胞交叉模态研究的必要性。总的来说,我们的研究证明了在细胞类型分类中对完整的单细胞解剖结构进行定量描述的关键需求,因为单细胞形态多样性揭示了不同细胞类型及其个体成员可能对结构和功能做出贡献的多种方式他们各自的电路。强调单细胞交叉模式研究的必要性。总的来说,我们的研究证明了在细胞类型分类中对完整的单细胞解剖结构进行定量描述的关键需求,因为单细胞形态多样性揭示了不同细胞类型及其个体成员可能对结构和功能做出贡献的多种方式他们各自的电路。强调单细胞交叉模式研究的必要性。总的来说,我们的研究证明了在细胞类型分类中对完整的单细胞解剖结构进行定量描述的关键需求,因为单细胞形态多样性揭示了不同细胞类型及其个体成员可能对结构和功能做出贡献的多种方式他们各自的电路。

更新日期:2021-10-06
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