Brain-wide correspondence of neuronal epigenomics and distant projections

Zhou, Jingtian and Zhang, Zhuzhu and Wu, May and Liu, Hanqing and Pang, Yan and Bartlett, Anna and Peng, Zihao and Ding, Wubin and Rivkin, Angeline and Lagos, Will N. and Williams, Elora and Lee, Cheng-Ta and Miyazaki, Paula Assakura and Aldridge, Andrew and Zeng, Qiurui and Salinda, J. L. Angelo and Claffey, Naomi and Liem, Michelle and Fitzpatrick, Conor and Boggeman, Lara and Yao, Zizhen and Smith, Kimberly A. and Tasic, Bosiljka and Altshul, Jordan and Kenworthy, Mia A. and Valadon, Cynthia and Nery, Joseph R. and Castanon, Rosa G. and Patne, Neelakshi S. and Vu, Minh and Rashid, Mohammad and Jacobs, Matthew and Ito, Tony and Osteen, Julia and Emerson, Nora and Lee, Jasper and Cho, Silvia and Rink, Jon and Huang, Hsiang-Hsuan and Pinto-Duartec, António and Dominguez, Bertha and Smith, Jared B. and O’Connor, Carolyn and Zeng, Hongkui and Chen, Shengbo and Lee, Kuo-Fen and Mukamel, Eran A. and Jin, Xin and Margarita Behrens, M. and Ecker, Joseph R. and Callaway, Edward M. (2023) Brain-wide correspondence of neuronal epigenomics and distant projections. Nature, 624 (7991). pp. 355-365. ISSN 0028-0836

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Abstract

Single-cell analyses parse the brain’s billions of neurons into thousands of ‘cell-type’ clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

Item Type: Article
Subjects: Open Research Librarians > Geological Science
Depositing User: Unnamed user with email support@open.researchlibrarians.com
Date Deposited: 14 Dec 2023 10:55
Last Modified: 14 Dec 2023 10:55
URI: http://stm.e4journal.com/id/eprint/2372

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