Comparative cellular analysis of motor cortex in human, marmoset and mouse

被引：371

作者：

Bakken, Trygve E. ^{[1
]}

Jorstad, Nikolas L. ^{[1
]}

Hu, Qiwen ^{[2
]}

Lake, Blue B. ^{[3
]}

Tian, Wei ^{[4
]}

Kalmbach, Brian E. ^{[1
,5
]}

Crow, Megan ^{[6
]}

Hodge, Rebecca D. ^{[1
]}

Krienen, Fenna M. ^{[7
]}

Sorensen, Staci A. ^{[1
]}

Eggermont, Jeroen ^{[8
]}

Yao, Zizhen ^{[1
]}

Aevermann, Brian D. ^{[9
]}

Aldridge, Andrew I. ^{[10
]}

Bartlett, Anna ^{[10
]}

Bertagnolli, Darren ^{[1
]}

Casper, Tamara ^{[1
]}

Castanon, Rosa G. ^{[10
]}

Crichton, Kirsten ^{[1
]}

Daigle, Tanya L. ^{[1
]}

Dalley, Rachel ^{[1
]}

Dee, Nick ^{[1
]}

Dembrow, Nikolai ^{[11
]}

Diep, Dinh ^{[3
]}

Ding, Song-Lin ^{[1
]}

Dong, Weixiu ^{[3
]}

Fang, Rongxin ^{[12
]}

Fischer, Stephan ^{[6
]}

Goldman, Melissa ^{[7
]}

Goldy, Jeff ^{[1
]}

Graybuck, Lucas T. ^{[1
]}

Herb, Brian R. ^{[13
]}

Hou, Xiaomeng ^{[14
]}

Kancherla, Jayaram ^{[15
]}

Kroll, Matthew ^{[1
]}

Lathia, Kanan ^{[1
]}

van Lew, Baldur ^{[6
]}

Li, Yang Eric ^{[14
,16
]}

Liu, Christine S.

Liu, Hanqing ^{[18
]}

Lucero, Jacinta D. ^{[10
]}

Mahurkar, Anup ^{[4
]}

McMillen, Delissa ^{[13
]}

Miller, Jeremy A. ^{[1
]}

Moussa, Marmar ^{[19
]}

Nery, Joseph R. ^{[10
]}

Nicovich, Philip R. ^{[1
]}

Niu, Sheng-Yong ^{[10
,20
]}

Orvis, Joshua ^{[13
]}

Osteen, Julia K. ^{[4
]}

机构：

[1] Allen Inst Brain Sci, Seattle, WA 98109 USA

[2] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[3] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[4] Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[5] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA

[6] Stanley Inst Cognit Genom, Cold Spring Harbor Lab, Cold Spring Harbor, NY USA

[7] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[8] Leiden Univ, Dept Radiol, LKEB, Med Ctr, Leiden, Netherlands

[9] J Craig Venter Inst, La Jolla, CA USA

[10] Salk Inst Biol Studies, Genom Anal Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[11] Epilepsy Ctr Excellence, Dept Vet Affairs Med Ctr, Seattle, WA USA

[12] Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, San Diego, CA 92103 USA

[13] Univ Maryland, Sch Med, Inst Genomes Sci, Baltimore, MD USA

[14] Univ Calif San Diego, Dept Cellular & Mol Med, Ctr Epigen, San Diego, CA 92103 USA

[15] Univ Maryland, Dept Comp Sci, College Pk, MD USA

[16] Ludwig Inst Canc Res, La Jolla, CA USA

[17] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA

[18] Univ Calif San Diego, Sch Med, Program Biomed Sci, San Diego, CA 92103 USA

[19] Univ Connecticut, Storrs, CT USA

[20] Univ Calif San Diego, Comp Sci & Engn Program, San Diego, CA 92103 USA

[21] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden

[22] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA

[23] Univ Calif San Diego, Dept Phys, San Diego, CA 92103 USA

[24] Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA

[25] Univ Maryland, Sch Med, Dept Otorhinolaryngol Anat & Neurobiol, Baltimore, MD USA

[26] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, Friedman Brain Inst, New York, NY USA

[27] Delt Univ Technol, Comp Graph & Visualizat Grp, Delft, Netherlands

[28] Univ Washington, Washington Natl Primate Res Ctr, Dept Physiol & Biophys, Seattle, WA 98195 USA

[29] Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA

[30] Univ Washington, Dept Neurol Surg, Sch Med, Seattle, WA 98195 USA

[31] Harborview Med Ctr, Reg Epilepsy Ctr, Seattle, WA USA

[32] Delft Univ Technol, Pattern Recognit & Bioinformat Grp, Delft, Netherlands

[33] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[34] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA

[35] Broad Inst MIT & Harvard, Cambridge, MA USA

[36] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA

[37] La Jolla Inst Immunol, Div Vaccine Discovery, La Jolla, CA USA

[38] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[39] MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[40] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[41] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

来源：

NATURE | 2021年 / 598卷 / 7879期

基金：

美国国家科学基金会; 美国国家卫生研究院; 荷兰研究理事会;

关键词：

PYRAMIDAL NEURONS; MORPHOLOGICAL PROPERTIES; CHROMATIN ACCESSIBILITY; MOLECULAR DIVERSITY; PREMOTOR CORTEX; ADULT; CLASSIFICATION; FREQUENCY; CELLS; EVOLUTION;

D O I：

10.1038/s41586-021-03465-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals(1). 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.

引用

页码：111 / +

页数：44

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