Morphological diversity of single neurons in molecularly defined cell types.

Peng, Hanchuan, Xie, Peng, Liu, Lijuan, Kuang, Xiuli, Wang, Yimin, Qu, Lei, Gong, Hui, Jiang, Shengdian, Li, Anan, Ruan, Zongcai, Ding, Liya, Yao, Zizhen, Chen, Chao, Chen, Mengya, Daigle, Tanya L, Dalley, Rachel, Ding, Zhangcan, Duan, Yanjun, Feiner, Aaron, He, Ping, Hill, Chris, Hirokawa, Karla E, Hong, Guodong, Huang, Lei, Kebede, Sara, Kuo, Hsien-Chi, Larsen, Rachael, Lesnar, Phil, Li, Longfei, Li, Qi, Li, Xiangning, Li, Yaoyao, Li, Yuanyuan, Liu, An, Lu, Donghuan, Mok, Stephanie, Ng, Lydia, Nguyen, Thuc Nghi, Ouyang, Qiang, Pan, Jintao, Shen, Elise, Song, Yuanyuan, Sunkin, Susan M, Tasic, Bosiljka, Veldman, Matthew B, Wakeman, Wayne, Wan, Wan, Wang, Peng, Wang, Quanxin, Wang, Tao, Wang, Yaping, Xiong, Feng, Xiong, Wei, Xu, Wenjie, Ye, Min, Yin, Lulu, Yu, Yang, Yuan, Jia, Yuan, Jing, Yun, Zhixi, Zeng, Shaoqun, Zhang, Shichen, Zhao, Sujun, Zhao, Zijun, Zhou, Zhi, Huang, Z Josh, Esposito, Luke, Hawrylycz, Michael J, Sorensen, Staci A, Yang, X William, Zheng, Yefeng, Gu, Zhongze, Xie, Wei, Koch, Christof, Luo, Qingming, Harris, Julie A, Wang, Yun, Zeng, Hongkui (October 2021) Morphological diversity of single neurons in molecularly defined cell types. Nature, 598 (7879). pp. 174-181. ISSN 0028-0836

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Abstract

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.

Item Type:	Paper
Subjects:	Investigative techniques and equipment Investigative techniques and equipment > assays organs, tissues, organelles, cell types and functions > organs types and functions > brain organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > tissues types and functions > neocortex organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions Investigative techniques and equipment > assays > RNA-seq organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Huang, Z. Josh
Communities:	CSHL labs > Huang lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	October 2021
Date Deposited:	13 Oct 2021 14:16
Last Modified:	25 Jan 2024 16:12
PMCID:	PMC8494643
URI:	https://repository.cshl.edu/id/eprint/40383

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