A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
Nature·2021365 cites
20212026
365
Yao, Zizhen and Liu, Hanqing and Xie, Fangming and Fischer, Stephan and Adkins, Ricky S. and Aldridge, Andrew I. and Ament, Seth A. and Bartlett, Anna and Behrens, M. Margarita and Van den Berge, Koen and Bertagnolli, Darren and de B{\'e}zieux, Hector Roux and Biancalani, Tommaso and Booeshaghi, A. Sina and Bravo, H{\'e}ctor Corrada and Casper, Tamara and Colantuoni, Carlo and Crabtree, Jonathan and Creasy, Heather and Crichton, Kirsten and Crow, Megan and Dee, Nick and Dougherty, Elizabeth L. and Doyle, Wayne I. and Dudoit, Sandrine and Fang, Rongxin and Felix, Victor and Fong, Olivia and Giglio, Michelle and Goldy, Jeff and Hawrylycz, Mike and Herb, Brian R. and Hertzano, Ronna and Hou, Xiaomeng and Hu, Qiwen and Kancherla, Jayaram and Kroll, Matthew and Lathia, Kanan and Li, Yang Eric and Lucero, Jacinta D. and Luo, Chongyuan and Mahurkar, Anup and McMillen, Delissa and Nadaf, Naeem M. and Nery, Joseph R. and Nguyen, Thuc Nghi and Niu, Sheng-Yong and Ntranos, Vasilis and Orvis, Joshua and Osteen, Julia K. and Pham, Thanh and Pinto-Duarte, Antonio and Poirion, Olivier and Preissl, Sebastian and Purdom, Elizabeth and Rimorin, Christine and Risso, Davide and Rivkin, Angeline C. and Smith, Kimberly and Street, Kelly and Sulc, Josef and Svensson, Valentine and Tieu, Michael and Torkelson, Amy and Tung, Herman and Vaishnav, Eeshit Dhaval and Vanderburg, Charles R. and van Velthoven, Cindy and Wang, Xinxin and White, Owen R. and Huang, Z. Josh and Kharchenko, Peter V. and Pachter, Lior and Ngai, John and Regev, Aviv and Tasic, Bosiljka and Welch, Joshua D. and Gillis, Jesse and Macosko, Evan Z. and Ren, Bing and Ecker, Joseph R. and Zeng, Hongkui and Mukamel, Eran A.
Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.
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