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Publication : Morphological diversity of single neurons in molecularly defined cell types.

First Author  Peng H Year  2021
Journal  Nature Volume  598
Issue  7879 Pages  174-181
PubMed ID  34616072 Mgi Jnum  J:325784
Mgi Id  MGI:7287826 Doi  10.1038/s41586-021-03941-1
Citation  Peng H, et al. (2021) Morphological diversity of single neurons in molecularly defined cell types. Nature 598(7879):174-181
abstractText  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.
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