A multimodal cell census and atlas of the mammalian primary motor cortex

BRAIN Initiative Cell Census Network (BICCN), , Adkins, Ricky, Aldridge, Andrew, Allen, Shona, Ament, Seth, An, Xu, Armand, Ethan, Ascoli, Giorgio, Bakken, Trygve, Bandrowski, Anita, Banerjee, Samik, Barkas, Nikolaos, Bartlett, Anna, Bateup, Helen, Behrens, Margarita, Berens, Philipp, Berg, Jim, Bernabucci, Matteo, Bernaerts, Yves, Bertagnolli, Darren, Biancalani, Tommaso, Boggeman, Lara, Booeshaghi, Sina, Bowman, Ian, Bravo, Héctor Corrada, Cadwell, Cathryn René, Callaway, Edward, Carlin, Benjamin, O'Connor, Carolyn, Carter, Robert, Casper, Tamara, Castanon, Rosa, Castro, Jesus Ramon, Chance, Rebecca, Chatterjee, Apaala, Chen, Huaming, Chun, Jerold, Colantuoni, Carlo, Crabtree, Jonathan, Creasy, Heather, Crichton, Kirsten, Crow, Megan, D'Orazi, Florence, Daigle, Tanya, Dalley, Rachel, Dee, Nick, Degatano, Kylee, Dichter, Benjamin, Diep, Dinh, Ding, Liya, Ding, Song-Lin, Dominguez, Bertha, Dong, Hong-Wei, Dong, Weixiu, Dougherty, Elizabeth, Dudoit, Sandrine, Ecker, Joseph, Eichhorn, Stephen, Fang, Rongxin, Felix, Victor, Feng, Guoping, Feng, Zhao, Fischer, Stephan, Fitzpatrick, Conor, Fong, Olivia, Foster, Nicholas, Galbavy, William, Gee, James, Ghosh, Satrajit, Giglio, Michelle, Gillespie, Thomas, Gillis, Jesse, Goldman, Melissa, Goldy, Jeff, Gong, Hui, Gou, Lin, Grauer, Michael, Halchenko, Yaroslav, Harris, Julie, Hartmanis, Leonard, Hatfield, Joshua, Hawrylycz, Mike, Helba, Brian, Herb, Brian, Hertzano, Ronna, Hintiryan, Houri, Hirokawa, Karla, Hockemeyer, Dirk, Hodge, Rebecca, Hood, Greg, Horwitz, Gregory, Hou, Xiaomeng, Hu, Lijuan, Hu, Qiwen, Huang, Josh, Huo, Bingxing, Ito-Cole, Tony, Jacobs, Matthew, Jia, Xueyan, Jiang, Shengdian, Jiang, Tao, Jiang, Xiaolong, Jin, Xin, Jorstad, Nikolas, Kalmbach, Brian, Kancherla, Jayaram, Keene, Dirk, Kelly, Kathleen, Khajouei, Farzaneh, Kharchenko, Peter, Kim, Gukhan, Ko, Andrew, Kobak, Dmitry, Konwar, Kishori, Kramer, Daniel, Krienen, Fenna, Kroll, Matthew, Kuang, Xiuli, Kuo, Hsien-Chi, Lake, Blue, Larsen, Rachael, Lathia, Kanan, Laturnus, Sophie, Lee, Angus, Lee, Cheng-Ta, Lee, Kuo-Fen, Lein, Ed, Lesnar, Phil, Li, Anan, Li, Xiangning, Li, Xu, Li, Yang Eric, Li, Yaoyao, Li, Yuanyuan, Lim, Byungkook, Linnarsson, Sten, Liu, Christine, Liu, Hanqing, Liu, Lijuan, Lucero, Jacinta, Luo, Chongyuan, Luo, Qingming, Macosko, Evan, Mahurkar, Anup, Martone, Maryann, Matho, Katherine, McCarroll, Steven, McCracken, Carrie, McMillen, Delissa, Miranda, Elanine, Mitra, Partha, Miyazaki, Paula Assakura, Mizrachi, Judith, Mok, Stephanie, Mukamel, Eran, Mulherkar, Shalaka, Nadaf, Naeem, Naeemi, Maitham, Narasimhan, Arun, Nery, Joseph, Ng, Lydia, Ngai, John, Nguyen, Thuc Nghi, Nickel, Lance, Nicovich, Philip, Niu, Sheng-Yong, Ntranos, Vasilis, Nunn, Michael, Olley, Dustin, Orvis, Joshua, Osteen, Julia, Osten, Pavel, Owen, Scott, Pachter, Lior, Palaniswamy, Ramesh, Palmer, Carter, Pang, Yan, Peng, Hanchuan, Pham, Thanh, Pinto-Duarte, Antonio, Plongthongkum, Nongluk, Poirion, Olivier, Preissl, Sebastian, Purdom, Elizabeth, Qu, Lei, Rashid, Mohammad, Reed, Nora, Regev, Aviv, Ren, Bing, Ren, Miao, Rimorin, Christine, Risso, Davide, Rivkin, Angeline, Muñoz-Castañeda, Rodrigo, Romanow, William, Ropelewski, Alexander, Roux de Bézieux, Hector, Ruan, Zongcai, Sandberg, Rickard, Savoia, Steven, Scala, Federico, Schor, Michael, Shen, Elise, Siletti, Kimberly, Smith, Jared, Smith, Kimberly, Somasundaram, Saroja, Song, Yuanyuan, Sorensen, Staci, Stafford, David, Street, Kelly, Sulc, Josef, Sunkin, Susan, Svensson, Valentine, Tan, Pengcheng, Tan, Zheng Huan, Tasic, Bosiljka, Thompson, Carol, Tian, Wei, Tickle, Timothy, Tieu, Michael, Ting, Jonathan, Tolias, Andreas Savas, Torkelson, Amy, Tung, Herman, Vaishnav, Eeshit Dhaval, Van den Berge, Koen, van Velthoven, Cindy TJ, Vanderburg, Charles, Veldman, Matthew, Vu, Minh, Wakeman, Wayne, Wang, Peng, Wang, Quanxin, Wang, Xinxin, Wang, Yimin, Wang, Yun, Welch, Joshua, White, Owen, Williams, Elora, Xie, Fangming, Xie, Peng, Xiong, Feng, Yang, William, Yanny, Anna Marie, Yao, Zizhen, Yin, Lulu, Yu, Yang, Yuan, Jing, Z, Hongkui (October 2020) A multimodal cell census and atlas of the mammalian primary motor cortex. BioRxiv. (Unpublished)

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DOI: 10.1101/2020.10.19.343129

Abstract

<h4>ABSTRACT</h4> We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) 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. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Item Type: Paper
Subjects: Investigative techniques and equipment > brain atlas
organism description > animal > mammal > primates > hominids > human
organism description > animal > mammal > primates > monkey
organs, tissues, organelles, cell types and functions > tissues types and functions > motor cortex
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
Investigative techniques and equipment > assays > Single cell sequencing
CSHL Authors:
Communities: CSHL labs > Gillis Lab
CSHL labs > Huang lab
CSHL labs > Mitra lab
CSHL labs > Osten lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 21 October 2020
Date Deposited: 06 May 2021 14:44
Last Modified: 06 May 2021 14:44
URI: https://repository.cshl.edu/id/eprint/40000

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