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An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types

Yao, Zizhen and Liu, Hanqing and Xie, Fangming and Fischer, Stephan and Adkins, Ricky S. and Aldrige, Andrew I. and Ament, Seth A. and Bartlett, Ann and Behrens, M. Margarita and Van den Berge, Koen and Bertagnolli, Darren and Biancalani, Tommaso and Booeshaghi, A. Sina and Corrada Bravo, Hector 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, Michael and Roux de Bezieux, Hector and Herb, Brian R. and Hertzano, Ronna and Hou, Xiaomeng and Hu, Qiwen and Huang, Z. Josh 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 and Gillis, Jesse and Kharchenko, Peter V. and Ngai, John and Pachter, Lior and Regev, Aviv and Tasic, Bosiljka and Welch, Joshua D. and Ecker, Joseph R. and Macosko, Evan and Ren, Bing and Zeng, Hongkui and Mukamel, Eran A. (2020) An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200303-153620082

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Abstract

Single cell transcriptomics has transformed the characterization of brain cell identity by providing quantitative molecular signatures for large, unbiased samples of brain cell populations. With the proliferation of taxonomies based on individual datasets, a major challenge is to integrate and validate results toward defining biologically meaningful cell types. We used a battery of single-cell transcriptome and epigenome measurements generated by the BRAIN Initiative Cell Census Network (BICCN) to comprehensively assess the molecular signatures of cell types in the mouse primary motor cortex (MOp). We further developed computational and statistical methods to integrate these multimodal data and quantitatively validate the reproducibility of the cell types. The reference atlas, based on more than 600,000 high quality single-cell or -nucleus samples assayed by six molecular modalities, is a comprehensive molecular account of the diverse neuronal and non-neuronal cell types in MOp. Collectively, our study indicates that the mouse primary motor cortex contains over 55 neuronal cell types that are highly replicable across analysis methods, sequencing technologies, and modalities. We find many concordant multimodal markers for each cell type, as well as thousands of genes and gene regulatory elements with discrepant transcriptomic and epigenomic signatures. These data highlight the complex molecular regulation of brain cell types and will directly enable design of reagents to target specific MOp cell types for functional analysis.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.02.29.970558DOIDiscussion Paper
https://assets.nemoarchive.org/dat-ch1nqb7Related ItemData/Code
https://nemoanalytics.org/Related ItemData/Code
https://brainome.ucsd.edu/annoj/BICCN_MOpRelated ItemData/Code
ORCID:
AuthorORCID
Yao, Zizhen0000-0002-9361-5607
Liu, Hanqing0000-0002-5114-6048
Xie, Fangming0000-0001-5232-1648
Fischer, Stephan0000-0002-7034-4103
Adkins, Ricky S.0000-0002-7983-5486
Aldrige, Andrew I.0000-0003-1962-8802
Ament, Seth A.0000-0001-6443-7509
Bartlett, Ann0000-0001-7059-4033
Behrens, M. Margarita0000-0002-7168-8186
Van den Berge, Koen0000-0002-1833-8478
Bertagnolli, Darren0000-0002-6626-1567
Biancalani, Tommaso0000-0001-9104-9755
Booeshaghi, A. Sina0000-0002-6442-4502
Corrada Bravo, Hector0000-0002-1255-4444
Casper, Tamara0000-0003-1638-3651
Colantuoni, Carlo0000-0001-6818-6380
Creasy, Heather0000-0002-1369-6882
Crichton, Kirsten0000-0002-7869-1492
Crow, Megan0000-0002-1172-5897
Dee, Nick0000-0002-2831-9254
Dougherty, Elizabeth L.0000-0001-8922-5078
Doyle, Wayne I.0000-0001-8276-2591
Dudoit, Sandrine0000-0002-6069-8629
Fang, Rongxin0000-0003-0107-7504
Felix, Victor0000-0002-9773-0629
Fong, Olivia0000-0002-7091-9667
Giglio, Michelle0000-0001-7628-5565
Goldy, Jeff0000-0001-5140-6922
Hawrylycz, Michael0000-0002-5741-8024
Roux de Bezieux, Hector0000-0002-1489-8339
Herb, Brian R.0000-0002-5910-9647
Hertzano, Ronna0000-0002-8093-6567
Hou, Xiaomeng0000-0002-5453-9015
Hu, Qiwen0000-0003-2798-919X
Huang, Z. Josh0000-0003-0592-028X
Kancherla, Jayaram0000-0001-5855-5031
Kroll, Matthew0000-0002-0126-7618
Lathia, Kanan0000-0003-0080-1951
Li, Yang Eric0000-0001-6997-6018
Lucero, Jacinta D.0000-0001-7578-6624
Luo, Chongyuan0000-0002-8541-0695
Mahurkar, Anup0000-0002-4999-2296
McMillen, Delissa0000-0002-3413-4424
Nadaf, Naeem M.0000-0002-7805-8523
Nery, Joseph R.0000-0003-0153-5659
Nguyen, Thuc Nghi0000-0002-6466-5883
Niu, Sheng-Yong0000-0002-7734-1191
Ntranos, Vasilis0000-0002-2477-0670
Orvis, Joshua0000-0002-5705-5710
Osteen, Julia K.0000-0001-7058-3297
Pham, Thanh0000-0002-4738-5062
Pinto-Duarte, Antonio0000-0002-2215-7653
Poirion, Olivier0000-0002-0429-7003
Preissl, Sebastian0000-0001-8971-5616
Purdom, Elizabeth0000-0001-9455-7990
Rimorin, Christine0000-0003-1491-8552
Risso, Davide0000-0001-8508-5012
Rivkin, Angeline C.0000-0003-0399-9043
Smith, Kimberly0000-0002-3142-1970
Street, Kelly0000-0001-6379-5013
Sulc, Josef0000-0002-4928-7183
Svensson, Valentine0000-0002-9217-2330
Tieu, Michael0000-0001-9286-5623
Torkelson, Amy0000-0002-9465-4202
Tung, Herman0000-0002-0812-3318
Vaishnav, Eeshit Dhaval0000-0003-3720-8051
Vanderburg, Charles R.0000-0001-8979-5054
van Velthoven, Cindy0000-0001-5120-4546
Wang, Xinxin0000-0001-6393-2276
White, Owen0000-0003-2407-7320
Gillis, Jesse0000-0002-0936-9774
Kharchenko, Peter V.0000-0002-6036-5875
Ngai, John0000-0002-1191-8971
Pachter, Lior0000-0002-9164-6231
Regev, Aviv0000-0003-3293-3158
Tasic, Bosiljka0000-0002-6861-4506
Welch, Joshua D.0000-0002-5869-2391
Ecker, Joseph R.0000-0001-5799-5895
Macosko, Evan0000-0002-2794-5165
Ren, Bing0000-0002-5435-1127
Zeng, Hongkui0000-0002-0326-5878
Mukamel, Eran A.0000-0003-3203-9535
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted March 02, 2020. We are grateful to Anita Bandrowski and Yong Yao for insightful comments. This work was funded by the NIH BRAIN Initiative (U19MH114830 to H.Z.; U19MH121282 to J.R.E.; U19MH114821 to Z.J.H.; R24MH114788 to O.R.W.; U24MH114827 to M.H.; R24MH114815 to R.H./O.R.W.; NIH NIDCD DC013817 to R.H.), the Hearing Restoration project Hearing Health Foundation (R.H.), and NIH NIGMS (GM114267 to H.C.B.). Author contributions: Contribution to RNA data generation: A.R., A.T., B.T., C.R., C.R.V., D.B., D.M., E.L.D., E.Z.M., H.T., H.Z., J.G., J.S., K.C., K.L., K.S., M.K., M.T., N.D., N.M.N., O.F., T.C., T.N.N., T.P. Contribution to mC data generation: A.B., A.C.R., A.I.A., A.P., C.L., H.L., J.D.L., J.K.O., J.R.E., J.R.N., M.M.B., S.N., Y.E.L. Contribution to ATAC data generation: A.P., B.R., J.D.L., J.K.O., M.M.B., S.P., X.H., X.W., Y.E.L. Contribution to data archive/infrastructure: A.M., B.R.H., C.C., C.V.V., E.A.M., F.X., H.C., H.C.B., J.C., J.G., J.K., J.O., M.G., M.H., O.R.W., R.F., R.H., R.S.A., S.A.A., S.N., V.F., W.I.D., Z.Y. Contribution to data analysis: A.R., A.S.B., B.T., D.R., E.A.M., E.D.V., E.P., E.Z.M., F.X., H.L., H.R.D.B., H.Z., J.D.W., J.G., J.G., J.O., K.S., K.S., K.V.D.B., L.P., M.C., O.F., O.P., P.V.K., Q.H., R.F., S.D., S.F., S.N., T.B., V.N., V.S., W.I.D., Y.E.L., Z.Y. Contribution to data interpretation: A.R., B.R., B.T., C.L., E.A.M., E.D.V., E.Z.M., F.X., H.L., H.Z., J.D.W., J.G., J.N., M.C., M.M.B., P.V.K., Q.H., R.F., S.F., T.B., Y.E.L., Z.Y. Contribution to writing manuscript: A.S.B., E.A.M., F.X., H.L., H.Z., J.D.W., J.G., L.P., M.C., Q.H., S.F., Z.J.H., Z.Y. Competing interests: B.R. is a share holder of Arima Genomics, Inc. P.V.K. serves on the Scientific Advisory Board to Celsius Therapeutics Inc. A.R. is an equity holder and founder of Celsius Therapeutics, an equity holder in Immunitas, and an SAB member in Syros Pharmaceuticals, Neogene Therapeutics, Asimov, and Thermo Fisher Scientific. Data access and analysis resource: The BICCN MOp data (RRID:SCR_015820) can be accessed via the NeMO archive (RRID:SCR_002001) at accession: https://assets.nemoarchive.org/dat-ch1nqb7. Visualization and analysis resources: NeMO analytics: https://nemoanalytics.org/, Genome browser: https://brainome.ucsd.edu/annoj/BICCN_MOp/, Epiviz browser: https://epiviz.nemoanalytics.org/biccn_mop.
Funders:
Funding AgencyGrant Number
NIHU19MH114830
NIHU19MH121282
NIHU19MH114821
NIHR24MH114788
NIHU24MH114827
NIHR24MH114815
NIHDC013817
Hearing Restoration project Hearing Health FoundationUNSPECIFIED
NIHGM114267
Record Number:CaltechAUTHORS:20200303-153620082
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200303-153620082
Official Citation:An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types. Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Ricky S Adkins, Andrew I Aldrige, Seth A Ament, Ann Bartlett, M. Margarita Behrens, Koen Van den Berge, Darren Bertagnolli, Tommaso Biancalani, A. Sina Booeshaghi, Hector Corrada Bravo, Tamara Casper, Carlo Colantuoni, Jonathan Crabtree, Heather Creasy, Kirsten Crichton, Megan Crow, Nick Dee, Elizabeth L Dougherty, Wayne I Doyle, Sandrine Dudoit, Rongxin Fang, Victor Felix, Olivia Fong, Michelle Giglio, Jeff Goldy, Michael Hawrylycz, Hector Roux de Bezieux, Brian R. Herb, Ronna Hertzano, Xiaomeng Hou, Qiwen Hu, Z. Josh Huang, Jayaram Kancherla, Matthew Kroll, Kanan Lathia, Yang Eric Li, Jacinta D. Lucero, Chongyuan Luo, Anup Mahurkar, Delissa McMillen, Naeem M. Nadaf, Joseph R. Nery, Thuc Nghi Nguyen, Sheng-Yong Niu, Vasilis Ntranos, Joshua Orvis, Julia K. Osteen, Thanh Pham, Antonio Pinto-Duarte, Olivier Poirion, Sebastian Preissl, Elizabeth Purdom, Christine Rimorin, Davide Risso, Angeline C. Rivkin, Kimberly Smith, Kelly Street, Josef Sulc, Valentine Svensson, Michael Tieu, Amy Torkelson, Herman Tung, Eeshit Dhaval Vaishnav, Charles R. Vanderburg, Cindy van Velthoven, Xinxin Wang, Owen White, Jesse Gillis, Peter V. Kharchenko, John Ngai, Lior Pachter, Aviv Regev, Bosiljka Tasic, Joshua D Welch, Joseph R. Ecker, Evan Macosko, Bing Ren, BRAIN Initiative Cell Census Network (BICCN), Hongkui Zeng, Eran A Mukamel. bioRxiv 2020.02.29.970558; doi: https://doi.org/10.1101/2020.02.29.970558
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101686
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:04 Mar 2020 19:50
Last Modified:04 Mar 2020 19:50

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