Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse
Author:
Bakken Trygve E.ORCID, Jorstad Nikolas L.ORCID, Hu QiwenORCID, Lake Blue B.ORCID, Tian WeiORCID, Kalmbach Brian E.ORCID, Crow MeganORCID, Hodge Rebecca D.ORCID, Krienen Fenna M.ORCID, Sorensen Staci A.ORCID, Eggermont JeroenORCID, Yao ZizhenORCID, Aevermann Brian D.ORCID, Aldridge Andrew I.ORCID, Bartlett AnnaORCID, Bertagnolli DarrenORCID, Casper TamaraORCID, Castanon Rosa G.ORCID, Crichton KirstenORCID, Daigle Tanya L.ORCID, Dalley RachelORCID, Dee NickORCID, Dembrow NikolaiORCID, Diep DinhORCID, Ding Song-LinORCID, Dong WeixiuORCID, Fang RongxinORCID, Fischer StephanORCID, Goldman MelissaORCID, Goldy JeffORCID, Graybuck Lucas T.ORCID, Herb Brian R.ORCID, Hou XiaomengORCID, Kancherla JayaramORCID, Kroll MatthewORCID, Lathia KananORCID, van Lew BaldurORCID, Li Yang EricORCID, Liu Christine S.ORCID, Liu HanqingORCID, Lucero Jacinta D.ORCID, Mahurkar AnupORCID, McMillen DelissaORCID, Miller Jeremy A.ORCID, Moussa MarmarORCID, Nery Joseph R.ORCID, Nicovich Philip R.ORCID, Orvis JoshuaORCID, Osteen Julia K.ORCID, Owen ScottORCID, Palmer Carter R.ORCID, Pham ThanhORCID, Plongthongkum NonglukORCID, Poirion OlivierORCID, Reed Nora M.ORCID, Rimorin ChristineORCID, Rivkin AngelineORCID, Romanow William J.ORCID, Sedeño-Cortés Adriana E.ORCID, Siletti KimberlyORCID, Somasundaram SarojaORCID, Sulc JosefORCID, Tieu MichaelORCID, Torkelson AmyORCID, Tung HermanORCID, Wang XinxinORCID, Xie FangmingORCID, Yanny Anna MarieORCID, Zhang ReneeORCID, Ament Seth A.ORCID, Behrens M. MargaritaORCID, Bravo Hector CorradaORCID, Chun JeroldORCID, Dobin AlexanderORCID, Gillis JesseORCID, Hertzano RonnaORCID, Hof Patrick R.ORCID, Höllt ThomasORCID, Horwitz Gregory D.ORCID, Keene C. DirkORCID, Kharchenko Peter V.ORCID, Ko Andrew L.ORCID, Lelieveldt Boudewijn P.ORCID, Luo ChongyuanORCID, Mukamel Eran A.ORCID, Preissl SebastianORCID, Regev AvivORCID, Ren BingORCID, Scheuermann Richard H.ORCID, Smith KimberlyORCID, Spain William J.ORCID, White Owen R.ORCID, Koch ChristofORCID, Hawrylycz MichaelORCID, Tasic BosiljkaORCID, Macosko Evan Z.ORCID, McCarroll Steven A.ORCID, Ting Jonathan T.ORCID, Zeng HongkuiORCID, Zhang KunORCID, Feng GuopingORCID, Ecker Joseph R.ORCID, Linnarsson StenORCID, Lein Ed S.ORCID
Abstract
AbstractThe primary motor cortex (M1) is essential for voluntary fine motor control and is functionally conserved across mammals. Using high-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, and mouse, we demonstrate a broadly conserved cellular makeup of this region, whose similarity mirrors evolutionary distance and is consistent between the transcriptome and epigenome. The core conserved molecular identity of neuronal and non-neuronal types allowed the generation of a cross-species consensus cell type classification and inference of conserved cell type properties across species. Despite overall conservation, many species specializations were apparent, including differences in cell type proportions, gene expression, DNA methylation, and chromatin state. Few cell type marker genes were conserved across species, providing a short list of candidate genes and regulatory mechanisms responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allowed the Patch-seq identification of layer 5 (L5) corticospinal Betz cells in non-human primate and human and characterization of their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell type diversity in M1 across mammals and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
Publisher
Cold Spring Harbor Laboratory
Cited by
42 articles.
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