A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yao, Z; Liu, H; Xie, F; Fischer, S; Adkins, RS; Aldridge, AI; Ament, SA; Bartlett, A; Behrens, MM; Van den Berge, K; Bertagnolli, D; de Bézieux, HR; Biancalani, T; Booeshaghi, AS; Bravo, HC; Casper, T; Colantuoni, C; Crabtree, J; Creasy, H; Crichton, K; Crow, M; Dee, N; Dougherty, EL; Doyle, WI; Dudoit, S; Fang, R; Felix, V; Fong, O; Giglio, M; Goldy, J; Hawrylycz, M; Herb, BR; Hertzano, R; Hou, X; Hu, Q; Kancherla, J; Kroll, M; Lathia, K; Li, YE; Lucero, JD; Luo, C; Mahurkar, A; McMillen, D; Nadaf, NM; Nery, JR; Nguyen, TN; Niu, S-Y; Ntranos, V; Orvis, J; Osteen, JK; Pham, T; Pinto-Duarte, A; Poirion, O; Preissl, S; Purdom, E; Rimorin, C; Risso, D; Rivkin, AC; Smith, K; Street, K; Sulc, J; Svensson, V; Tieu, M; Torkelson, A; Tung, H; Vaishnav, ED; Vanderburg, CR; van Velthoven, C; Wang, X; White, OR; Huang, ZJ; Kharchenko, PV; Pachter, L; Ngai, J; Regev, A; Tasic, B; Welch, JD; Gillis, J; Macosko, EZ; Ren, B; Ecker, JR; Zeng, H; Mukamel, EA

Published Date

  • October 2021

Published In

Volume / Issue

  • 598 / 7879

Start / End Page

  • 103 - 110

PubMed ID

  • 34616066

Pubmed Central ID

  • PMC8494649

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-021-03500-8

Language

  • eng

Conference Location

  • England