A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.
Zizhen YaoHanqing LiuFangming XieStephan FischerRicky S AdkinsAndrew I AldridgeSeth A AmentAnna BartlettM Margarita BehrensKoen Van den BergeDarren BertagnolliHector Roux de BezieuxTommaso BiancalaniAli Sina BooeshaghiHéctor Corrada BravoTamara CasperCarlo ColantuoniJonathan CrabtreeHeather H CreasyKirsten CrichtonMegan CrowNick DeeElizabeth L DoughertyWayne I DoyleSandrine DudoitRongxin FangVictor FelixOlivia FongMichelle G GiglioJeff GoldyMichael J HawrylyczBrian R HerbRonna HertzanoXiaomeng HouQiwen HuJayaram KancherlaMatthew KrollKanan LathiaYang Eric LiJacinta D LuceroChongyuan LuoAnup A MahurkarDelissa McMillenNaeem M NadafJoseph R NeryThuc Nghi NguyenSheng-Yong NiuVasilis NtranosJoshua OrvisJulia K OsteenTrangthanh H PhamAntónio Pinto-DuarteOlivier PoirionSebastian PreisslElizabeth PurdomChristine RimorinDavide RissoAngeline C RivkinKimberly A SmithKelly StreetJosef SulcValentine SvenssonMichael TieuAmy TorkelsonHerman TungEeshit Dhaval VaishnavCharles R VanderburgCindy T J van VelthovenXinxin WangOwen R WhiteZ Josh HuangPeter V KharchenkoLior PachterJohn NgaiAviv RegevBosiljka TasicJoshua D WelchJesse GillisEvan Z MacoskoBing RenJoseph R EckerHongkui ZengEran A MukamelPublished in: Nature (2021)
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.