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Morphological diversity of single neurons in molecularly defined cell types.

Publication ,  Journal Article
Peng, H; Xie, P; Liu, L; Kuang, X; Wang, Y; Qu, L; Gong, H; Jiang, S; Li, A; Ruan, Z; Ding, L; Yao, Z; Chen, C; Chen, M; Daigle, TL; He, P ...
Published in: Nature
October 2021

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 2021

Volume

598

Issue

7879

Start / End Page

174 / 181

Location

England

Related Subject Headings

  • Single-Cell Analysis
  • Reproducibility of Results
  • RNA-Seq
  • Neurons
  • Neuroglia
  • Neurogenesis
  • Neocortex
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Developmental
 

Citation

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Peng, H., Xie, P., Liu, L., Kuang, X., Wang, Y., Qu, L., … Zeng, H. (2021). Morphological diversity of single neurons in molecularly defined cell types. Nature, 598(7879), 174–181. https://doi.org/10.1038/s41586-021-03941-1
Peng, Hanchuan, Peng Xie, Lijuan Liu, Xiuli Kuang, Yimin Wang, Lei Qu, Hui Gong, et al. “Morphological diversity of single neurons in molecularly defined cell types.Nature 598, no. 7879 (October 2021): 174–81. https://doi.org/10.1038/s41586-021-03941-1.
Peng H, Xie P, Liu L, Kuang X, Wang Y, Qu L, et al. Morphological diversity of single neurons in molecularly defined cell types. Nature. 2021 Oct;598(7879):174–81.
Peng, Hanchuan, et al. “Morphological diversity of single neurons in molecularly defined cell types.Nature, vol. 598, no. 7879, Oct. 2021, pp. 174–81. Pubmed, doi:10.1038/s41586-021-03941-1.
Peng H, Xie P, Liu L, Kuang X, Wang Y, Qu L, Gong H, Jiang S, Li A, Ruan Z, Ding L, Yao Z, Chen C, Chen M, Daigle TL, Dalley R, Ding Z, Duan Y, Feiner A, He P, Hill C, Hirokawa KE, Hong G, Huang L, Kebede S, Kuo H-C, Larsen R, Lesnar P, Li L, Li Q, Li X, Li Y, Liu A, Lu D, Mok S, Ng L, Nguyen TN, Ouyang Q, Pan J, Shen E, Song Y, Sunkin SM, Tasic B, Veldman MB, Wakeman W, Wan W, Wang P, Wang Q, Wang T, Xiong F, Xiong W, Xu W, Ye M, Yin L, Yu Y, Yuan J, Yun Z, Zeng S, Zhang S, Zhao S, Zhao Z, Zhou Z, Huang ZJ, Esposito L, Hawrylycz MJ, Sorensen SA, Yang XW, Zheng Y, Gu Z, Xie W, Koch C, Luo Q, Harris JA, Zeng H. Morphological diversity of single neurons in molecularly defined cell types. Nature. 2021 Oct;598(7879):174–181.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 2021

Volume

598

Issue

7879

Start / End Page

174 / 181

Location

England

Related Subject Headings

  • Single-Cell Analysis
  • Reproducibility of Results
  • RNA-Seq
  • Neurons
  • Neuroglia
  • Neurogenesis
  • Neocortex
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Developmental