@article{8760939,
  abstract     = {{Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization<jats:sup>1–5</jats:sup>. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.</jats:p>}},
  author       = {{Callaway, Edward M. and Dong, Hong-Wei and Ecker, Joseph R. and Hawrylycz, Michael J. and Huang, Z. Josh and Lein, Ed S. and Ngai, John and Osten, Pavel and Ren, Bing and Tolias, Andreas Savas and White, Owen and Zeng, Hongkui and Zhuang, Xiaowei and Ascoli, Giorgio A. and Behrens, M. Margarita and Chun, Jerold and Feng, Guoping and Gee, James C. and Ghosh, Satrajit S. and Halchenko, Yaroslav O. and Hertzano, Ronna and Lim, Byung Kook and Martone, Maryann E. and Ng, Lydia and Pachter, Lior and Ropelewski, Alexander J. and Tickle, Timothy L. and Yang, X. William and Zhang, Kun and Bakken, Trygve E. and Berens, Philipp and Daigle, Tanya L. and Harris, Julie A. and Jorstad, Nikolas L. and Kalmbach, Brian E. and Kobak, Dmitry and Li, Yang Eric and Liu, Hanqing and Matho, Katherine S. and Mukamel, Eran A. and Naeemi, Maitham and Scala, Federico and Tan, Pengcheng and Ting, Jonathan T. and Xie, Fangming and Zhang, Meng and Zhang, Zhuzhu and Zhou, Jingtian and Zingg, Brian and Armand, Ethan and Yao, Zizhen and Bertagnolli, Darren and Casper, Tamara and Crichton, Kirsten and Dee, Nick and Diep, Dinh and Ding, Song-Lin and Dong, Weixiu and Dougherty, Elizabeth L. and Fong, Olivia and Goldman, Melissa and Goldy, Jeff and Hodge, Rebecca D. and Hu, Lijuan and Keene, C. Dirk and Krienen, Fenna M. and Kroll, Matthew and Lake, Blue B. and Lathia, Kanan and Linnarsson, Sten and Liu, Christine S. and Macosko, Evan Z. and McCarroll, Steven A. and McMillen, Delissa and Nadaf, Naeem M. and Nguyen, Thuc Nghi and Palmer, Carter R. and Pham, Thanh and Plongthongkum, Nongluk and Reed, Nora M. and Regev, Aviv and Rimorin, Christine and Romanow, William J. and Savoia, Steven and Siletti, Kimberly and Smith, Kimberly and Sulc, Josef and Tasic, Bosiljka and Tieu, Michael and Torkelson, Amy and Tung, Herman and van Velthoven, Cindy T. J. and Vanderburg, Charles R. and Yanny, Anna Marie and Fang, Rongxin and Hou, Xiaomeng and Lucero, Jacinta D. and Osteen, Julia K. and Pinto-Duarte, Antonio and Poirion, Olivier and Preissl, Sebastian and Wang, Xinxin and Aldridge, Andrew I. and Bartlett, Anna and Boggeman, Lara and O’Connor, Carolyn and Castanon, Rosa G. and Chen, Huaming and Fitzpatrick, Conor and Luo, Chongyuan and Nery, Joseph R. and Nunn, Michael and Rivkin, Angeline C. and Tian, Wei and Dominguez, Bertha and Ito-Cole, Tony and Jacobs, Matthew and Jin, Xin and Lee, Cheng-Ta and Lee, Kuo-Fen and Miyazaki, Paula Assakura and Pang, Yan and Rashid, Mohammad and Smith, Jared B. and Vu, Minh and Williams, Elora and Biancalani, Tommaso and Booeshaghi, A. Sina and Crow, Megan and Dudoit, Sandrine and Fischer, Stephan and Gillis, Jesse and Hu, Qiwen and Kharchenko, Peter V. and Niu, Sheng-Yong and Ntranos, Vasilis and Purdom, Elizabeth and Risso, Davide and de Bézieux, Hector Roux and Somasundaram, Saroja and Street, Kelly and Svensson, Valentine and Vaishnav, Eeshit Dhaval and Van den Berge, Koen and Welch, Joshua D. and An, Xu and Bateup, Helen S. and Bowman, Ian and Chance, Rebecca K. and Foster, Nicholas N. and Galbavy, William and Gong, Hui and Gou, Lin and Hatfield, Joshua T. and Hintiryan, Houri and Hirokawa, Karla E. and Kim, Gukhan and Kramer, Daniel J. and Li, Anan and Li, Xiangning and Luo, Qingming and Muñoz-Castañeda, Rodrigo and Stafford, David A. and Feng, Zhao and Jia, Xueyan and Jiang, Shengdian and Jiang, Tao and Kuang, Xiuli and Larsen, Rachael and Lesnar, Phil and Li, Yaoyao and Li, Yuanyuan and Liu, Lijuan and Peng, Hanchuan and Qu, Lei and Ren, Miao and Ruan, Zongcai and Shen, Elise and Song, Yuanyuan and Wakeman, Wayne and Wang, Peng and Wang, Yimin and Wang, Yun and Yin, Lulu and Yuan, Jing and Zhao, Sujun and Zhao, Xuan and Narasimhan, Arun and Palaniswamy, Ramesh and Banerjee, Samik and Ding, Liya and Huilgol, Dhananjay and Huo, Bingxing and Kuo, Hsien-Chi and Laturnus, Sophie and Li, Xu and Mitra, Partha P. and Mizrachi, Judith and Wang, Quanxin and Xie, Peng and Xiong, Feng and Yu, Yang and Eichhorn, Stephen W. and Berg, Jim and Bernabucci, Matteo and Bernaerts, Yves and Cadwell, Cathryn René and Castro, Jesus Ramon and Dalley, Rachel and Hartmanis, Leonard and Horwitz, Gregory D. and Jiang, Xiaolong and Ko, Andrew L. and Miranda, Elanine and Mulherkar, Shalaka and Nicovich, Philip R. and Owen, Scott F. and Sandberg, Rickard and Sorensen, Staci A. and Tan, Zheng Huan and Allen, Shona and Hockemeyer, Dirk and Lee, Angus Y. and Veldman, Matthew B. and Adkins, Ricky S. and Ament, Seth A. and Bravo, Héctor Corrada and Carter, Robert and Chatterjee, Apaala and Colantuoni, Carlo and Crabtree, Jonathan and Creasy, Heather and Felix, Victor and Giglio, Michelle and Herb, Brian R. and Kancherla, Jayaram and Mahurkar, Anup and McCracken, Carrie and Nickel, Lance and Olley, Dustin and Orvis, Joshua and Schor, Michael and Hood, Greg and Dichter, Benjamin and Grauer, Michael and Helba, Brian and Bandrowski, Anita and Barkas, Nikolaos and Carlin, Benjamin and D’Orazi, Florence D. and Degatano, Kylee and Gillespie, Thomas H. and Khajouei, Farzaneh and Konwar, Kishori and Thompson, Carol and Kelly, Kathleen and Mok, Stephanie and Sunkin, Susan and BRAIN Initiative Cell Census Network (BICCN) Corresponding authors, [missing] and BICCN contributing principal investigators, [missing] and Principal manuscript editors, [missing] and Manuscript writing and figure generation, [missing] and Analysis coordination, [missing] and Integrated data analysis, [missing] and scRNA-seq and snRNA-seq data generation and processing, [missing] and ATAC-seq data generation and processing, [missing] and Methylcytosine data production and analysis, [missing] and Epi-retro-seq data generation and processing, [missing] and ‘Omics data analysis, [missing] and Tracing and connectivity data generation, [missing] and Morphology data generation and reconstruction, [missing] and OLST/STPT and other data generation, [missing] and Morphology, connectivity and imaging analysis, [missing] and Spatially resolved single-cell transcriptomics (MERFISH), [missing] and Multimodal profiling (Patch-seq), [missing] and Transgenic tools, [missing] and NeMO archive and analytics, [missing] and Brain Image Library (BIL) archive, [missing] and DANDI archive, [missing] and Brain Cell Data Center (BCDC), [missing] and Project management, [missing] and BRAIN Initiative Cell Census Network (BICCN), [missing]}},
  issn         = {{0028-0836}},
  journal      = {{NATURE}},
  keywords     = {{Multidisciplinary,SINGLE,MOUSE,TRANSCRIPTOMICS,SPECIFICATION,PATHWAYS,NEURONS,CLASSIFICATION,ORGANIZATION,INTERNEURONS,MORPHOLOGY}},
  language     = {{eng}},
  number       = {{7879}},
  pages        = {{86--102}},
  title        = {{A multimodal cell census and atlas of the mammalian primary motor cortex}},
  url          = {{http://doi.org/10.1038/s41586-021-03950-0}},
  volume       = {{598}},
  year         = {{2021}},
}

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