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

Adkins, Ricky S. and Aldridge, Andrew I. and Allen, Shona and Ament, Seth A. and An, Xu and Armand, Ethan and Ascoli, Giorgio A. and Bakken, Trygve E. and Bandrowski, Anita and Banerjee, Samik and Barkas, Nikolaos and Bartlett, Anna and Bateup, Helen S. and Behrens, M. Margarita and Berens, Philipp and Berg, Jim and Bernabucci, Matteo and Bernaerts, Yves and Bertagnolli, Darren and Biancalani, Tommaso and Boggeman, Lara and Booeshaghi, A. Sina and Bowman, Ian and Bravo, Héctor Corrada and Cadwell, Cathryn René and Callaway, Edward M. and Carlin, Benjamin and O'Connor, Carolyn and Carter, Robert and Casper, Tamara and Castanon, Rosa G. and Castro, Jesus Ramon and Chance, Rebecca K. and Chatterjee, Apaala and Chen, Huaming and Chun, Jerold and Colantuoni, Carlo and Crabtree, Jonathan and Creasy, Heather and Crichton, Kirsten and Crow, Megan and D'Orazi, Florence D. and Daigle, Tanya L. and Dalley, Rachel and Dee, Nick and Degatano, Kylee and Dichter, Benjamin and Diep, Dinh and Ding, Liya and Ding, Song-Lin and Dominguez, Bertha and Dong, Hong-Wei and Dong, Weixiu and Dougherty, Elizabeth L. and Dudoit, Sandrine and Ecker, Joseph R. and Eichhorn, Stephen W. and Fang, Rongxin and Felix, Victor and Feng, Guoping and Feng, Zhao and Fischer, Stephan and Fitzpatrick, Conor and Fong, Olivia and Foster, Nicholas N. and Galbavy, William and Gee, James C. and Ghosh, Satrajit S. and Giglio, Michelle and Gillespie, Thomas H. and Gillis, Jesse and Goldman, Melissa and Goldy, Jeff and Gong, Hui and Gou, Lin and Grauer, Michael and Halchenko, Yaroslav O. and Harris, Julie A. and Hartmanis, Leonard and Hatfield, Joshua T. and Hawrylycz, Mike and Helba, Brian and Herb, Brian R. and Hertzano, Ronna and Hintiryan, Houri and Hirokawa, Karla E. and Hockemeyer, Dirk and Hodge, Rebecca D. and Hood, Greg and Horwitz, Gregory D. and Hou, Xiaomeng and Hu, Lijuan and Hu, Qiwen and Huang, Z. Josh and Huo, Bingxing and Ito-Cole, Tony and Jacobs, Matthew and Jia, Xueyan and Jiang, Shengdian and Jiang, Tao and Jiang, Xiaolong and Jin, Xin and Jorstad, Nikolas L. and Kalmbach, Brian E. and Kancherla, Jayaram and Keene, C. Dirk and Kelly, Kathleen and Khajouei, Farzaneh and Kharchenko, Peter V. and Kim, Gukhan and Ko, Andrew L. and Kobak, Dmitry and Konwar, Kishori and Kramer, Daniel J. and Krienen, Fenna M. and Kroll, Matthew and Kuang, Xiuli and Kuo, Hsien-Chi and Lake, Blue B. and Larsen, Rachael and Lathia, Kanan and Laturnus, Sophie and Lee, Angus Y. and Lee, Cheng-Ta and Lee, Kuo-Fen and Lein, Ed S. and Lesnar, Phil and Li, Anan and Li, Xiangning and Li, Xu and Li, Yang Eric and Li, Yaoyao and Li, Yuanyuan and Lim, Byungkook and Linnarsson, Sten and Liu, Christine S. and Liu, Hanqing and Liu, Lijuan and Lucero, Jacinta D. and Luo, Chongyuan and Luo, Qingming and Macosko, Evan Z. and Mahurkar, Anup and Martone, Maryann E. and Matho, Katherine S. and McCarroll, Steven A. and McCracken, Carrie and McMillen, Delissa and Miranda, Elanine and Mitra, Partha P and Miyazaki, Paula Assakura and Mizrachi, Judith and Mok, Stephanie and Mukamel, Eran A. and Mulherkar, Shalaka and Nadaf, Naeem M. and Naeemi, Maitham and Narasimhan, Arun and Nery, Joseph R. and Ng, Lydia and Ngai, John and Nguyen, Thuc Nghi and Nickel, Lance and Nicovich, Philip R. and Niu, Sheng-Yong and Ntranos, Vasilis and Nunn, Michael and Olley, Dustin and Orvis, Joshua and Osteen, Julia K. and Osten, Pavel and Owen, Scott F. and Pachter, Lior and Palaniswamy, Ramesh and Palmer, Carter R. and Pang, Yan and Peng, Hanchuan and Pham, Thanh and Pinto-Duarte, Antonio and Plongthongkum, Nongluk and Poirion, Olivier and Preissl, Sebastian and Purdom, Elizabeth and Qu, Lei and Rashid, Mohammad and Reed, Nora M. and Regev, Aviv and Ren, Bing and Ren, Miao and Rimorin, Christine and Risso, Davide and Rivkin, Angeline C. and Muñoz-Castañeda, Rodrigo and Romanow, William J. and Ropelewski, Alexander J. and Roux de Bézieux, Hector and Ruan, Zongcai and Sandberg, Rickard and Savoia, Steven and Scala, Federico and Schor, Michael and Shen, Elise and Siletti, Kimberly and Smith, Jared B. and Smith, Kimberly and Somasundaram, Saroja and Song, Yuanyuan and Sorensen, Staci A. and Stafford, David A. and Street, Kelly and Sulc, Josef and Sunkin, Susan and Svensson, Valentine and Tan, Pengcheng and Tan, Zheng Huan and Tasic, Bosiljka and Thompson, Carol and Tian, Wei and Tickle, Timothy L. and Tieu, Michael and Ting, Jonathan T. and Tolias, Andreas Savas and Torkelson, Amy and Tung, Herman and Vaishnav, Eeshit Dhaval and Van den Berge, Koen and van Velthoven, Cindy T.J. and Vanderburg, Charles R. and Veldman, Matthew B. and Vu, Minh and Wakeman, Wayne and Wang, Peng and Wang, Quanxin and Wang, Xinxin and Wang, Yimin and Wang, Yun and Welch, Joshua D. and White, Owen and Williams, Elora and Xie, Fangming and Xie, Peng and Xiong, Feng and Yang, X. William and Yanny, Anna Marie and Yao, Zizhen and Yin, Lulu and Yu, Yang and Yuan, Jing and Zeng, Hongkui and Zhang, Kun and Zhang, Meng and Zhang, Zhuzhu and Zhao, Sujun and Zhao, Xuan and Zhou, Jingtian and Zhuang, Xiaowei and Zingg, Brian (2021) A multimodal cell census and atlas of the mammalian primary motor cortex. Nature, 598 (7879). pp. 86-102. ISSN 0028-0836. doi:10.1038/s41586-021-03950-0. https://resolver.caltech.edu/CaltechAUTHORS:20201027-075126222

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Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20201027-075126222

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. 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41586-021-03950-0DOIArticle
https://doi.org/10.1101/2020.10.19.343129DOIDiscussion Paper
https://doi.org/10.5281/zenodo.4726182DOIData
https://github.com/BICCN/CellCensusMotorCortexRelated Itemcode
ORCID:
AuthorORCID
Adkins, Ricky S.0000-0002-7983-5486
Aldridge, Andrew I.0000-0003-1962-8802
Allen, Shona0000-0003-0186-0574
Ament, Seth A.0000-0001-6443-7509
An, Xu0000-0003-3386-5521
Armand, Ethan0000-0002-4516-6317
Ascoli, Giorgio A.0000-0002-0964-676X
Bakken, Trygve E.0000-0003-3373-7386
Bandrowski, Anita0000-0002-5497-0243
Banerjee, Samik0000-0003-2325-1489
Barkas, Nikolaos0000-0002-4675-0718
Bartlett, Anna0000-0001-7059-4033
Bateup, Helen S.0000-0002-0135-0972
Behrens, M. Margarita0000-0002-7168-8186
Berens, Philipp0000-0002-0199-4727
Berg, Jim0000-0002-3300-5399
Bernabucci, Matteo0000-0003-4458-117X
Bernaerts, Yves0000-0003-4948-0423
Bertagnolli, Darren0000-0002-6626-1567
Biancalani, Tommaso0000-0001-9104-9755
Booeshaghi, A. Sina0000-0002-6442-4502
Bowman, Ian0000-0001-7366-9192
Bravo, Héctor Corrada0000-0002-1255-4444
Cadwell, Cathryn René0000-0003-1963-8285
Callaway, Edward M.0000-0002-6366-5267
Carlin, Benjamin0000-0002-9360-9143
O'Connor, Carolyn0000-0002-3301-7912
Carter, Robert0000-0003-0937-8141
Casper, Tamara0000-0003-1638-3651
Castanon, Rosa G.0000-0003-1791-002X
Castro, Jesus Ramon0000-0002-6628-980X
Chance, Rebecca K.0000-0001-7059-6119
Chatterjee, Apaala0000-0003-1170-8971
Chen, Huaming0000-0001-5289-7882
Chun, Jerold0000-0003-3964-0921
Colantuoni, Carlo0000-0001-6818-6380
Crabtree, Jonathan0000-0002-7286-5690
Creasy, Heather0000-0002-1369-6882
Crichton, Kirsten0000-0002-7869-1492
Crow, Megan0000-0002-1172-5897
D'Orazi, Florence D.0000-0002-7354-4725
Daigle, Tanya L.0000-0001-9700-8452
Dalley, Rachel0000-0001-7461-7845
Dee, Nick0000-0002-2831-9254
Degatano, Kylee0000-0002-0945-3300
Dichter, Benjamin0000-0001-5725-6910
Diep, Dinh0000-0001-6057-4119
Ding, Liya0000-0002-1209-875X
Ding, Song-Lin0000-0002-7072-5272
Dominguez, Bertha0000-0002-9470-7300
Dong, Hong-Wei0000-0001-9972-3177
Dong, Weixiu0000-0003-1059-5653
Dougherty, Elizabeth L.0000-0001-8922-5078
Dudoit, Sandrine0000-0002-6069-8629
Ecker, Joseph R.0000-0001-5799-5895
Eichhorn, Stephen W.0000-0002-6410-4699
Fang, Rongxin0000-0003-0107-7504
Felix, Victor0000-0002-9773-0629
Feng, Guoping0000-0002-8021-277X
Feng, Zhao0000-0001-5035-7655
Fischer, Stephan0000-0002-7034-4103
Fitzpatrick, Conor0000-0003-2625-6277
Fong, Olivia0000-0002-7091-9667
Foster, Nicholas N.0000-0003-1740-9788
Galbavy, William0000-0003-0948-9538
Gee, James C.0000-0002-2258-0187
Ghosh, Satrajit S.0000-0002-5312-6729
Giglio, Michelle0000-0001-7628-5565
Gillespie, Thomas H.0000-0002-7509-4801
Gillis, Jesse0000-0002-0936-9774
Goldman, Melissa0000-0003-1469-5360
Goldy, Jeff0000-0001-5140-6922
Gong, Hui0000-0001-5519-6248
Gou, Lin0000-0002-3109-1879
Grauer, Michael0000-0002-4167-1076
Halchenko, Yaroslav O.0000-0003-3456-2493
Harris, Julie A.0000-0003-0820-2021
Hartmanis, Leonard0000-0002-4922-8781
Hatfield, Joshua T.0000-0002-1639-7212
Hawrylycz, Mike0000-0002-5741-8024
Helba, Brian0000-0003-2628-805X
Herb, Brian R.0000-0002-5910-9647
Hertzano, Ronna0000-0002-8093-6567
Hintiryan, Houri0000-0002-9721-6785
Hirokawa, Karla E.0000-0002-9954-5515
Hockemeyer, Dirk0000-0002-5598-5092
Hodge, Rebecca D.0000-0002-5784-9668
Hood, Greg0000-0001-9871-7154
Horwitz, Gregory D.0000-0001-5130-5259
Hou, Xiaomeng0000-0002-5453-9015
Hu, Lijuan0000-0003-1869-0372
Hu, Qiwen0000-0003-2798-919X
Huang, Z. Josh0000-0003-0592-028X
Huo, Bingxing0000-0002-9389-2591
Ito-Cole, Tony0000-0001-5898-3108
Jacobs, Matthew0000-0002-3004-8553
Jia, Xueyan0000-0002-1221-6357
Jiang, Shengdian0000-0002-2277-263X
Jiang, Tao0000-0002-4487-299X
Jiang, Xiaolong0000-0001-8066-1383
Jin, Xin0000-0002-1106-4013
Jorstad, Nikolas L.0000-0001-7906-9470
Kalmbach, Brian E.0000-0003-3136-8097
Kancherla, Jayaram0000-0001-5855-5031
Keene, C. Dirk0000-0002-5291-1469
Kelly, Kathleen0000-0003-2334-9785
Khajouei, Farzaneh0000-0002-0148-9122
Kharchenko, Peter V.0000-0002-6036-5875
Kim, Gukhan0000-0002-3338-5045
Ko, Andrew L.0000-0002-6253-9891
Kobak, Dmitry0000-0002-5639-7209
Konwar, Kishori0000-0001-5152-4777
Kramer, Daniel J.0000-0003-4241-3586
Krienen, Fenna M.0000-0002-1400-6820
Kroll, Matthew0000-0002-0126-7618
Kuang, Xiuli0000-0001-7569-7605
Kuo, Hsien-Chi0000-0002-0215-2302
Lake, Blue B.0000-0002-8637-9044
Larsen, Rachael0000-0003-0178-003X
Lathia, Kanan0000-0003-0080-1951
Laturnus, Sophie0000-0001-9532-788X
Lee, Angus Y.0000-0002-7649-2705
Lee, Cheng-Ta0000-0001-6183-2319
Lee, Kuo-Fen0000-0003-2224-2708
Lein, Ed S.0000-0001-9012-6552
Lesnar, Phil0000-0002-2152-604X
Li, Anan0000-0002-5877-4813
Li, Xiangning0000-0002-3747-2824
Li, Yang Eric0000-0001-6997-6018
Li, Yaoyao0000-0001-5468-9876
Li, Yuanyuan0000-0002-0897-5270
Lim, Byungkook0000-0002-3766-5415
Linnarsson, Sten0000-0002-3491-3444
Liu, Christine S.0000-0002-1239-4612
Liu, Hanqing0000-0002-5114-6048
Liu, Lijuan0000-0002-9548-6183
Lucero, Jacinta D.0000-0001-7578-6624
Luo, Chongyuan0000-0002-8541-0695
Luo, Qingming0000-0002-6725-9311
Macosko, Evan Z.0000-0002-2794-5165
Mahurkar, Anup0000-0002-4999-2296
Martone, Maryann E.0000-0002-8406-3871
Matho, Katherine S.0000-0002-6105-4219
McCarroll, Steven A.0000-0002-6954-8184
McCracken, Carrie0000-0002-8038-9727
McMillen, Delissa0000-0002-3413-4424
Miranda, Elanine0000-0002-1633-9303
Mitra, Partha P0000-0001-8818-6804
Miyazaki, Paula Assakura0000-0003-1295-8710
Mizrachi, Judith0000-0003-2195-8210
Mok, Stephanie0000-0002-2688-1569
Mukamel, Eran A.0000-0003-3203-9535
Mulherkar, Shalaka0000-0001-8736-527X
Nadaf, Naeem M.0000-0002-7805-8523
Naeemi, Maitham0000-0001-9139-3548
Narasimhan, Arun0000-0002-0246-6301
Nery, Joseph R.0000-0003-0153-5659
Ng, Lydia0000-0002-7499-3514
Ngai, John0000-0002-1191-8971
Nguyen, Thuc Nghi0000-0002-6466-5883
Nickel, Lance0000-0002-5836-3571
Nicovich, Philip R.0000-0002-8517-4469
Niu, Sheng-Yong0000-0002-7734-1191
Ntranos, Vasilis0000-0002-2477-0670
Nunn, Michael0000-0002-6771-9912
Olley, Dustin0000-0001-8685-0839
Orvis, Joshua0000-0002-5705-5710
Osteen, Julia K.0000-0001-7058-3297
Osten, Pavel0000-0002-6385-7541
Owen, Scott F.0000-0001-6294-7513
Pachter, Lior0000-0002-9164-6231
Palaniswamy, Ramesh0000-0003-4322-2407
Palmer, Carter R.0000-0002-2385-2068
Pang, Yan0000-0003-3323-5052
Peng, Hanchuan0000-0002-3478-3942
Pham, Thanh0000-0002-4738-5062
Pinto-Duarte, Antonio0000-0002-2215-7653
Plongthongkum, Nongluk0000-0002-1305-285X
Poirion, Olivier0000-0002-0429-7003
Preissl, Sebastian0000-0001-8971-5616
Purdom, Elizabeth0000-0001-9455-7990
Qu, Lei0000-0002-2129-5253
Rashid, Mohammad0000-0002-7884-4954
Reed, Nora M.0000-0003-0408-1568
Regev, Aviv0000-0003-3293-3158
Ren, Bing0000-0002-5435-1127
Ren, Miao0000-0002-5555-5279
Rimorin, Christine0000-0003-1491-8552
Risso, Davide0000-0001-8508-5012
Rivkin, Angeline C.0000-0003-0399-9043
Muñoz-Castañeda, Rodrigo0000-0002-1176-7421
Romanow, William J.0000-0002-3808-6482
Ropelewski, Alexander J.0000-0001-6874-4477
Roux de Bézieux, Hector0000-0002-1489-8339
Ruan, Zongcai0000-0003-1547-165X
Sandberg, Rickard0000-0001-6473-1740
Savoia, Steven0000-0003-4514-7367
Scala, Federico0000-0002-2680-8572
Schor, Michael0000-0002-4493-7992
Shen, Elise0000-0002-3295-3928
Siletti, Kimberly0000-0001-7620-8973
Smith, Jared B.0000-0002-0273-4898
Smith, Kimberly0000-0002-3142-1970
Somasundaram, Saroja0000-0002-3729-9849
Song, Yuanyuan0000-0002-9183-5884
Sorensen, Staci A.0000-0002-6799-2126
Stafford, David A.0000-0002-3310-5402
Street, Kelly0000-0001-6379-5013
Sulc, Josef0000-0002-4928-7183
Sunkin, Susan0000-0001-9893-3834
Svensson, Valentine0000-0002-9217-2330
Tan, Pengcheng0000-0001-7276-0381
Tan, Zheng Huan0000-0002-1886-2421
Tasic, Bosiljka0000-0002-6861-4506
Thompson, Carol0000-0003-1528-3237
Tian, Wei0000-0002-2146-1717
Tickle, Timothy L.0000-0002-6592-6272
Tieu, Michael0000-0001-9286-5623
Ting, Jonathan T.0000-0001-8266-0392
Tolias, Andreas Savas0000-0002-4305-6376
Torkelson, Amy0000-0002-9465-4202
Tung, Herman0000-0002-0812-3318
Vaishnav, Eeshit Dhaval0000-0003-3720-8051
Van den Berge, Koen0000-0002-1833-8478
van Velthoven, Cindy T.J.0000-0001-5120-4546
Vanderburg, Charles R.0000-0001-8979-5054
Veldman, Matthew B.0000-0002-0328-5916
Vu, Minh0000-0003-4154-5659
Wakeman, Wayne0000-0002-3693-3609
Wang, Peng0000-0003-1181-5558
Wang, Quanxin0000-0002-0007-7935
Wang, Xinxin0000-0001-6393-2276
Wang, Yimin0000-0003-2515-6602
Wang, Yun0000-0001-5501-8433
Welch, Joshua D.0000-0002-5869-2391
White, Owen0000-0003-2407-7320
Williams, Elora0000-0002-0178-5511
Xie, Fangming0000-0001-5232-1648
Xie, Peng0000-0002-9509-7268
Xiong, Feng0000-0002-6927-8903
Yang, X. William0000-0003-3705-7935
Yanny, Anna Marie0000-0001-7250-8450
Yao, Zizhen0000-0002-9361-5607
Yin, Lulu0000-0003-2932-6349
Yu, Yang0000-0002-4340-430X
Yuan, Jing0000-0001-9050-4496
Zeng, Hongkui0000-0002-0326-5878
Zhang, Kun0000-0002-7596-5224
Zhang, Meng0000-0002-9753-0635
Zhang, Zhuzhu0000-0002-2661-4700
Zhao, Sujun0000-0001-7807-7495
Zhao, Xuan0000-0002-5778-5422
Zhou, Jingtian0000-0003-2060-1922
Zhuang, Xiaowei0000-0002-6034-7853
Zingg, Brian0000-0001-8657-8863
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 04 October 2020; Accepted 25 August 2021; Published 06 October 2021. We thank additional members of our laboratories and institutions who contributed to the experimental and analytical components of this project. This work was supported by grants from the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under: U24MH114827, U19MH114821, U19MH114830, U19MH114831, U01MH117072, U01MH114829, U01MH121282, U01MH117023, U01MH114825, U01MH114819, U01MH114812, U01MH121260, U01MH114824, U01MH117079, U01MH116990, U01MH114828, R24MH117295, R24MH114793, R24MH114788, R24MH114815. We thank NIH BICCN program officers, in particular Yong Yao, for their guidance and support throughout this study. Additional support: NIH grants R01NS39600 and R01NS86082 to G.A.A. H.S.B. is a Chan Zuckerberg Biohub Investigator. Deutsche Forschungsgemeinschaft through a Heisenberg Professorship (BE5601/4-1), the Cluster of Excellence Machine Learning—New Perspectives for Science (EXC 2064, project number 390727645) and the Collaborative Research Center 1233 Robust Vision (project number 276693517), the German Federal Ministry of Education and Research (FKZ 01GQ1601 and 01IS18039A) to P.B. This work was supported in part by the Flow Cytometry Core Facility of the Salk Institute with funding from NIH-NCI CCSG: P30 014195 and Shared Instrumentation Grant S10-OD023689. NIH grant R01MH094360 to H.-W.D. We thank M. Becerra, T. Boesen, C. Cao, M. Fayzullina, K. Cotter, L. Gao, L. Gacia, L. Korobkova, D. Lo, C. Mun, S. Yamashita and M Zhu for their technical and informatics support. Hearing Health Foundation Hearing Restoration Project grant to R.H. NIH grant OD010425 to G.D.H. NIH grant RF1MH114126 to E.S.L. and J.T.T. National Natural Science Foundation of China (NNSFC) grant 61890953 to H.G. NNSFC grant 81827901 to Q.L. This project was supported in part by NIH grants P51OD010425 from the Office of Research Infrastructure Programs (ORIP) and UL1TR000423 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH, ORIP, NCATS or the Institute of Translational Health Sciences at the Washington National Primate Research Center. NNSFC grant 61871411 and the University Synergy Innovation Program of Anhui Province GXXT-2019-008 to L.Q. Howard Hughes Medical Institute and the Klarman Cell Observatory for A.R. Howard Hughes Medical Institute for J.R.E. and X. Zhuang. NNSFC Grant 32071367 and NSF Shanghai Grant 20ZR1420100 to Yimin Wang. NIH grants R01EY023173 and U01MH105982 to H.Z. Researchers from Allen Institute for Brain Science wish to thank the Allen Institute founder, P. G. Allen, for his vision, encouragement and support. Data availability: Primary data are accessible through the Brain Cell Data Center and data archives. Brain Cell Data Center (BCDC), Overall BICCN organization and data, www.biccn.org. Neuroscience Multi-omic Data Archive (NeMO), RRID:SCR_016152. Brain Image Library (BIL), RRID:SCR_017272. Distributed Archives for Neurophysiology Data Integration (DANDI), RRID:SCR_017571. Publicly used databases in study: NCBI Homologene, 11/22/2019, https://www.ncbi.nlm.nih.gov/homologene, GENCODE mm10 (v16), https://www.gencodegenes.org, JASPAR 2020 database, http://jaspar.genereg.net. All data resources associated with this publication are available as listed at: https://github.com/BICCN/CellCensusMotorCortex and https://doi.org/10.5281/zenodo.4726182. Code availability: All code and libraries used in the manuscript are available at https://github.com/BICCN/CellCensusMotorCortex and https://doi.org/10.5281/zenodo.4726182. Author Contributions: BICCN contributing principal investigators: G.A.A., M.M.B., E.M.C., J. Chun, J.R.E., G.F., J.C.G., S.S.G., Y.O.H., M.J.H., R.H., H.-W.D., Z.J.H., E.S.L., B.K.L., M.E.M., L. Ng, P.O., L.P., A.J.R., T.L.T., A.S.T., O.W., X.W.Y., H.Z., K.Z., X. Zhuang and J.N. Principal manuscript editors: Z.J.H., E.S.L. and H.Z. Manuscript writing and figure generation: G.A.A., T.E.B., P.B., E.M.C., T.L.D., J.A.H., J.R.E., M.J.H., H.-W.D., Z.J.H., N.L.J., B.E.K., D.K., E.S.L., Y.E.L., H.L., K.S.M., E.A.M., M. Naeemi, B.Z., P.O., B.R., F.S., P.T., J.T.T., A.S.T., F. Xie, H.Z., M.Z., Z.Z., J.Z., X. Zhuang and J.N. Analysis coordination: T.E.B., E.M.C., J.A.H., J.R.E., M.J.H., H.-W.D., Z.J.H., E.S.L., E.A.M., P.O., B.R., A.S.T., H.Z., X. Zhuang and J.N. Integrated data analysis: E.A., T.E.B., P.B., J.A.H., J.R.E., H.-W.D., Z.J.H., N.L.J., B.E.K., D.K., E.S.L., Y.E.L., H.L., E.A.M., P.O., B.R., F.S., P.T., A.S.T., F. Xie, Z.Y., H.Z., M.Z., Z.Z., J.Z. and X. Zhuang. scRNA-seq and snRNA-seq data generation and processing: D.B., T.N.N., T.C., J. Chun, K.C., N.D., D.D., S.D., W.D., E.L.D., G.F., O.F., M. Goldman, J. Goldy, R.D.H., L. Hu, C.D.K., F.M.K., M.K., B.B.L., K.L., E.S.L., S. Linnarsson, C.S.L., E.Z.M., S.A.M., D.M., N.M.N., C.R.P., T.P., N.P., N.M.R., A.R., C.R., W.J.R., S. Savoia, K. Siletti, K. Smith, J.S., B.T., M.T., A.T., H.T., C.T.J.v.V., C.R.V., A.M.Y., H.Z. and K.Z. ATAC-seq data generation and processing: M.M.B., J. Chun, D.D., W.D., R.F., X.H., B.B.L., Y.E.L., C.S.L., J.D.L., J.K.O., C.R.P., A.P.-D., N.P., O.P., S.P., B.R., W.J.R., X.W. and K.Z. Methylcytosine data production and analysis: A.I.A., A. Bartlett, M.M.B., L.B., C.O., R.G.C., H.C., J.R.E., C.F., C.L., H.L., J.D.L., J.R.N., M. Nunn, J.K.O., A.P.-D., A.C.R., W.T. and J.Z. Epi-retro-seq data generation and processing: A. Bartlett, M.M.B., L.B., E.M.C., C.O., R.G.C., B. Dominguez, J.R.E., C.F., T.I.-C., M.J., X. Jin, C.L., K.L., P.A.M., E.A.M., J.R.N., M. Nunn, Y.P., A.P.-D., M. Rashid, A.C.R., J.B.S., P.T., M.V., E.W., Z.Z. and J.Z. ‘Omics data analysis: E.A., T.E.B., T.B., A.S.B., M.C., D.D., S.D., J.R.E., R.F., S.F., O.F., J. Gillis, J. Goldy, Q.H., N.L.J., P.V.K., F.M.K., B.B.L., E.S.L., Y.E.L., S. Linnarsson, H.L., E.Z.M., E.A.M., S.-Y.N., V.N., L.P., O.P., E.P., A.R., D.R., H.R.d.B., K. Siletti, K. Smith, S. Somasundaram, K. Street, V.S., B.T., W.T., E.D.V., K.V.d.B., C.T.J.v.V., J.D.W., F. Xie, Z.Y., H.Z., J.Z. and J.N. Tracing and connectivity data generation: X.A., H.S.B., R.K.C., J.A.H., K.E.H., W.G., H.G., J.T.H., I.B., H.-W.D., Z.J.H., G.K., D.J.K., A.L., Xiangning Li, B.K.L., Q.L., K.S.M., L. Ng, L.G., H.H., B.Z., R.M.-C., D.A.S., H.Z. and J.N. Morphology data generation and reconstruction: T.L.D., J.A.H., Z.F., K.E.H., H.G., H.-W.D., Z.J.H., X. Jia, S.J., T.J., X.K., R.L., P.L., Xiangning Li, Yaoyao Li, Yuanyuan Li, L.L., Q.L., H.P., L.Q., M. Ren, Z.R., E.S., Y.S., W.W., P.W., Yimin Wang, Yun Wang, L.Y., J.Y., H.Z., S.Z. and X. Zhao. OLST/STPT and other data generation: X.A., W.G., J.T.H., Z.J.H., G.K., K.S.M., A.N., P.O., R.P. and R.M.-C. Morphology, connectivity and imaging analysis: X.A., G.A.A., S.B., L.D., J.A.H., Z.F., W.G., H.G., J.T.H., H.-W.D., Z.J.H., D. Huilgol, B. Huo, X. Jia, G.K., H.-C.K., S. Laturnus, A.L., Xu Li, N.N.F., K.S.M., P.P.M., J.M., M. Naeemi, A.N., L. Ng, P.O., R.P., H.P., R.M.-C., Q.W., Yimin Wang, Yun Wang, P.X., F. Xiong, Y.Y. and H.Z. Spatially resolved single-cell transcriptomics (MERFISH): M.Z., S.W.E., B.Z., Z.Y., H.Z., H.-W.D. and X. Zhuang. Multimodal profiling (Patch-seq): P.B., J.B., M.B., Y.B., C.R.C., J.R.C., R.D., P.R.N., L. Hartmanis, G.D.H., X. Jiang, B.E.K., C.D.K., A.L.K., D.K., S. Laturnus, E.S.L., E.M., S. Mulherkar, S.F.O., R.S., F.S., K. Smith, S.A.S., Z.H.T., J.T.T., A.S.T. and H.Z. Transgenic tools: S.A., X.A., H.S.B., R.K.C., T.L.D., W.G., J.T.H., D. Hockemeyer, Z.J.H., D. Huilgol, G.K., D.J.K., A.Y.L., K.S.M., D.A.S., B.T., M.B.V., X.W.Y., Z.Y., H.Z. and J.N. NeMO archive and analytics: R.S.A., S.A.A., H.C.B., R.C., A.C., C.C., J. Crabtree, H.C., V.F., M. Giglio, B.R.H., R.H., J.K., A.M., C.M., L. Nickel, D.O., J.O., M.S. and O.W. Brain Image Library (BIL) archive: G.H. and A.J.R. DANDI archive: B. Dichter, S.S.G., M. Grauer, Y.O.H. and B. Helba. Brain Cell Data Center (BCDC): A. Bandrowski, N.B., B.C., F.D.D., K.D., J.C.G., T.H.G., M.J.H., F.K., K. Konwar, M.E.M., L. Ng, C.T. and T.L.T. Project management: F.D.D., H.G., K. Kelly, B.B.L., K.S.M., S. Mok, H.H., M. Nunn, S. Sunkin and C.T. Manuscript correspondence: H.Z. Competing interests: A. Bandrowski is a cofounder of SciCrunch, a company devoted to improving scientific communication. J.R.E. is a member of Zymo Research SAB. J.A.H., K.E.H., T.N.N. and P.R.N. are currently employed by Cajal Neuroscience. P.V.K. serves on the Scientific Advisory Board of Celsius Therapeutics Inc. M.E.M. is a founder and CSO of SciCrunch Inc., a UCSD tech start up that produces tools in support of reproducibility including RRIDs. A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics and until 31 August 2020 was a member of the scientific advisory board of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and ThermoFisher Scientific. From 1 August 2020, A.R. has been an employee of Genentech. B.R. is a co-founder of Arima Genomics, Inc. and Epigenome Technologies, Inc. K.Z. is a co-founder, equity holder and serves on the Scientific Advisor Board of Singlera Genomics. X. Zhuang is a co-founder and consultant of Vizgen. Peer review information: Nature thanks Peter Jones, Manolis Kellis and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.
Funders:
Funding AgencyGrant Number
NIHU24MH114827
NIHU19MH114821
NIHU19MH114830
NIHU19MH114831
NIHU01MH117072
NIHU01MH114829
NIHU01MH121282
NIHU01MH117023
NIHU01MH114825
NIHU01MH114819
NIHU01MH114812
NIHU01MH121260
NIHU01MH114824
NIHU01MH117079
NIHU01MH116990
NIHU01MH114828
NIHR24MH117295
NIHR24MH114793
NIHR24MH114788
NIHR24MH114815
NIHR01NS39600
NIHR01NS86082
Chan Zuckerberg InitiativeUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)BE5601/4-1
Deutsche Forschungsgemeinschaft (DFG)EXC 2064
Deutsche Forschungsgemeinschaft (DFG)390727645
Deutsche Forschungsgemeinschaft (DFG)276693517
Bundesministerium für Bildung und Forschung (BMBF)FKZ 01GQ1601
Bundesministerium für Bildung und Forschung (BMBF)FKZ 01IS18039A
NIHP30 014195
NIHS10-OD023689
NIHR01MH094360
NIHOD010425
NIHRF1MH114126
National Natural Science Foundation of China61890953
National Natural Science Foundation of China81827901
NIHP51OD010425
NIHUL1TR000423
National Natural Science Foundation of China61871411
Anhui ProvinceGXXT-2019-008
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Klarman Cell ObservatoryUNSPECIFIED
National Natural Science Foundation of China32071367
National Natural Science Foundation of China20ZR1420100
NIHR01EY023173
NIHU01MH105982
Allen Institute for Brain ScienceUNSPECIFIED
Salk InstituteUNSPECIFIED
Subject Keywords:Cellular neuroscience; Molecular neuroscience; Motor cortex; Neural circuits
Issue or Number:7879
DOI:10.1038/s41586-021-03950-0
Record Number:CaltechAUTHORS:20201027-075126222
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201027-075126222
Official Citation:BRAIN Initiative Cell Census Network (BICCN). A multimodal cell census and atlas of the mammalian primary motor cortex. Nature 598, 86–102 (2021). https://doi.org/10.1038/s41586-021-03950-0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106288
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:27 Oct 2020 17:28
Last Modified:29 Oct 2021 18:35

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