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Comparative cellular analysis of motor cortex in human, marmoset and mouse
Nature ( IF 64.8 ) Pub Date : 2021-10-06 , DOI: 10.1038/s41586-021-03465-8
Trygve E Bakken ₁ , Nikolas L Jorstad ₁ , Qiwen Hu ₂ , Blue B Lake ₃ , Wei Tian ₄ , Brian E Kalmbach _{1,

5} , Megan Crow ₆ , Rebecca D Hodge ₁ , Fenna M Krienen ₇ , Staci A Sorensen ₁ , Jeroen Eggermont ₈ , Zizhen Yao ₁ , Brian D Aevermann ₉ , Andrew I Aldridge ₁₀ , Anna Bartlett ₁₀ , Darren Bertagnolli ₁ , Tamara Casper ₁ , Rosa G Castanon ₁₀ , Kirsten Crichton ₁ , Tanya L Daigle ₁ , Rachel Dalley ₁ , Nick Dee ₁ , Nikolai Dembrow _{5,

11} , Dinh Diep ₃ , Song-Lin Ding ₁ , Weixiu Dong ₃ , Rongxin Fang ₁₂ , Stephan Fischer ₆ , Melissa Goldman ₇ , Jeff Goldy ₁ , Lucas T Graybuck ₁ , Brian R Herb ₁₃ , Xiaomeng Hou ₁₄ , Jayaram Kancherla ₁₅ , Matthew Kroll ₁ , Kanan Lathia ₁ , Baldur van Lew ₈ , Yang Eric Li _{14,

16} , Christine S Liu _{17,

18} , Hanqing Liu ₁₀ , Jacinta D Lucero ₄ , Anup Mahurkar ₁₃ , Delissa McMillen ₁ , Jeremy A Miller ₁ , Marmar Moussa ₁₉ , Joseph R Nery ₁₀ , Philip R Nicovich ₁ , Sheng-Yong Niu _{10,

20} , Joshua Orvis ₁₃ , Julia K Osteen ₄ , Scott Owen ₁ , Carter R Palmer _{17,

18} , Thanh Pham ₁ , Nongluk Plongthongkum ₃ , Olivier Poirion ₁₄ , Nora M Reed ₇ , Christine Rimorin ₁ , Angeline Rivkin ₄ , William J Romanow ₁₇ , Adriana E Sedeño-Cortés ₁ , Kimberly Siletti ₂₁ , Saroja Somasundaram ₁ , Josef Sulc ₁ , Michael Tieu ₁ , Amy Torkelson ₁ , Herman Tung ₁ , Xinxin Wang ₂₂ , Fangming Xie ₂₃ , Anna Marie Yanny ₁ , Renee Zhang ₉ , Seth A Ament ₁₃ , M Margarita Behrens ₄ , Hector Corrada Bravo ₁₅ , Jerold Chun ₁₇ , Alexander Dobin ₂₄ , Jesse Gillis ₆ , Ronna Hertzano ₂₅ , Patrick R Hof ₂₆ , Thomas Höllt ₂₇ , Gregory D Horwitz ₂₈ , C Dirk Keene ₂₉ , Peter V Kharchenko ₂ , Andrew L Ko _{30,

31} , Boudewijn P Lelieveldt _{8,

32} , Chongyuan Luo ₃₃ , Eran A Mukamel ₃₄ , António Pinto-Duarte ₄ , Sebastian Preissl ₁₄ , Aviv Regev ₃₅ , Bing Ren _{14,

16} , Richard H Scheuermann _{9,

36,

37} , Kimberly Smith ₁ , William J Spain _{5,

11} , Owen R White ₁₃ , Christof Koch ₁ , Michael Hawrylycz ₁ , Bosiljka Tasic ₁ , Evan Z Macosko ₃₅ , Steven A McCarroll _{7,

35} , Jonathan T Ting _{1,

5} , Hongkui Zeng ₁ , Kun Zhang ₃ , Guoping Feng _{38,

39,

40} , Joseph R Ecker _{10,

41} , Sten Linnarsson ₂₁ , Ed S Lein ₁

Affiliation

Allen Institute for Brain Science, Seattle, WA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
The Salk Institute for Biological Studies, La Jolla, CA, USA.
Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
LKEB, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
J. Craig Venter Institute, La Jolla, CA, USA.
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Epilepsy Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA, USA.
Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Institute for Genomes Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Department of Computer Science, University of Maryland College Park, College Park, MD, USA.
Ludwig Institute for Cancer Research, La Jolla, CA, USA.
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
University of Connecticut, Storrs, CT, USA.
Computer Science and Engineering Program, University of California, San Diego, La Jolla, CA, USA.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Department of Physics, University of California, San Diego, La Jolla, CA, USA.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Departments of Otorhinolaryngology, Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Computer Graphics and Visualization Group, Delt University of Technology, Delft, The Netherlands.
Department of Physiology and Biophysics, Washington National Primate Research Center, University of Washington, Seattle, WA, USA.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA.
Regional Epilepsy Center, Harborview Medical Center, Seattle, WA, USA.
Pattern Recognition and Bioinformatics group, Delft University of Technology, Delft, The Netherlands.
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Pathology, University of California, San Diego, CA, USA.
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals¹. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize 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.

中文翻译：

人类、狨猴和小鼠运动皮层的比较细胞分析

初级运动皮层 (M1) 对于自主精细运动控制至关重要，并且在哺乳动物中具有保守的功能¹。在这里，我们利用人类、狨猴和小鼠中超过 450,000 个单核的高通量转录组和表观基因组分析，证明了该区域广泛保守的细胞组成，其相似性反映了进化距离，并且转录组和表观基因组之间是一致的。神经元和非神经元细胞类型的核心保守分子身份使我们能够对细胞类型进行跨物种共识分类，并推断跨物种细胞类型的保守特性。然而，尽管整体保守，但许多物种依赖性的特化是明显的，包括细胞类型比例、基因表达、DNA 甲基化和染色质状态的差异。很少有细胞类型标记基因在物种之间是保守的，这揭示了负责同源细胞类型（例如 GABA 能吊灯细胞）保守特征的候选基因和调控机制的简短列表。这种一致的转录组学分类使我们能够使用 patch-seq（全细胞膜片钳记录、RNA 测序和形态学表征的组合）来识别非人类灵长类动物和人类中第 5 层的皮质脊髓 Betz 细胞，并表征其高度专门的生理学和解剖学。这些发现强调了哺乳动物 M1 细胞类型多样性的强大分子基础，并指出了负责细胞类型功能特性及其物种特异性适应的基因和调控途径。

更新日期：2021-10-06

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