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Nature

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Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.
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Información

Tipo de recurso:

revistas

ISSN impreso

0028-0836

ISSN electrónico

1476-4687

Editor responsable

Springer Nature

País de edición

Reino Unido

Fecha de publicación

Tabla de contenidos

Quantum anomalous Hall octet driven by orbital magnetism in bilayer graphene

Fabian R. GeisenhofORCID; Felix WintererORCID; Anna M. Seiler; Jakob Lenz; Tianyi Xu; Fan ZhangORCID; R. Thomas WeitzORCID

Palabras clave: Multidisciplinary.

Pp. 53-58

Topological complex-energy braiding of non-Hermitian bands

Kai WangORCID; Avik DuttORCID; Charles C. WojcikORCID; Shanhui FanORCID

Palabras clave: Multidisciplinary.

Pp. 59-64

Colorimetric histology using plasmonically active microscope slides

Eugeniu BalaurORCID; Sandra O’ Toole; Alex J. Spurling; G. Bruce Mann; Belinda Yeo; Kate Harvey; Catherine SadatnajafiORCID; Eric HanssenORCID; Jacqueline Orian; Keith A. NugentORCID; Belinda S. ParkerORCID; Brian AbbeyORCID

Palabras clave: Multidisciplinary.

Pp. 65-71

A crystalline tri-thorium cluster with σ-aromatic metal–metal bonding

Josef T. BoronskiORCID; John A. SeedORCID; David HungerORCID; Adam W. Woodward; Joris van SlagerenORCID; Ashley J. Wooles; Louise S. NatrajanORCID; Nikolas Kaltsoyannis; Stephen T. LiddleORCID

Palabras clave: Multidisciplinary.

Pp. 72-75

Mastering the surface strain of platinum catalysts for efficient electrocatalysis

Tianou He; Weicong Wang; Fenglei Shi; Xiaolong Yang; Xiang Li; Jianbo WuORCID; Yadong YinORCID; Mingshang JinORCID

Palabras clave: Multidisciplinary.

Pp. 76-81

Hemispheric black carbon increase after the 13th-century Māori arrival in New Zealand

Joseph R. McConnellORCID; Nathan J. Chellman; Robert Mulvaney; Sabine Eckhardt; Andreas Stohl; Gill PlunkettORCID; Sepp Kipfstuhl; Johannes Freitag; Elisabeth Isaksson; Kelly E. Gleason; Sandra O. Brugger; David B. McWethy; Nerilie J. AbramORCID; Pengfei Liu; Alberto J. Aristarain

Palabras clave: Multidisciplinary.

Pp. 82-85

A multimodal cell census and atlas of the mammalian primary motor cortex

; Edward M. Callaway; Hong-Wei Dong; Joseph R. Ecker; Michael J. Hawrylycz; Z. Josh Huang; Ed S. Lein; John Ngai; Pavel Osten; Bing Ren; Andreas Savas Tolias; Owen White; Hongkui ZengORCID; Xiaowei Zhuang; Giorgio A. Ascoli; M. Margarita Behrens; Jerold Chun; Guoping Feng; James C. Gee; Satrajit S. Ghosh; Yaroslav O. Halchenko; Ronna Hertzano; Byung Kook Lim; Maryann E. Martone; Lydia Ng; Lior Pachter; Alexander J. Ropelewski; Timothy L. Tickle; X. William Yang; Kun Zhang; Trygve E. Bakken; Philipp Berens; Tanya L. Daigle; Julie A. Harris; Nikolas L. Jorstad; Brian E. Kalmbach; Dmitry Kobak; Yang Eric Li; Hanqing Liu; Katherine S. Matho; Eran A. Mukamel; Maitham Naeemi; Federico Scala; Pengcheng Tan; Jonathan T. Ting; Fangming Xie; Meng Zhang; Zhuzhu Zhang; Jingtian Zhou; Brian Zingg; Ethan Armand; Zizhen Yao; Darren Bertagnolli; Tamara Casper; Kirsten Crichton; Nick Dee; Dinh Diep; Song-Lin Ding; Weixiu Dong; Elizabeth L. Dougherty; Olivia Fong; Melissa Goldman; Jeff Goldy; Rebecca D. Hodge; Lijuan Hu; C. Dirk Keene; Fenna M. Krienen; Matthew Kroll; Blue B. Lake; Kanan Lathia; Sten Linnarsson; Christine S. Liu; Evan Z. Macosko; Steven A. McCarroll; Delissa McMillen; Naeem M. Nadaf; Thuc Nghi Nguyen; Carter R. Palmer; Thanh Pham; Nongluk Plongthongkum; Nora M. Reed; Aviv Regev; Christine Rimorin; William J. Romanow; Steven Savoia; Kimberly Siletti; Kimberly Smith; Josef Sulc; Bosiljka Tasic; Michael Tieu; Amy Torkelson; Herman Tung; Cindy T. J. van Velthoven; Charles R. Vanderburg; Anna Marie Yanny; Rongxin Fang; Xiaomeng Hou; Jacinta D. Lucero; Julia K. Osteen; Antonio Pinto-Duarte; Olivier Poirion; Sebastian Preissl; Xinxin Wang; Andrew I. Aldridge; Anna Bartlett; Lara Boggeman; Carolyn O’Connor; Rosa G. Castanon; Huaming Chen; Conor Fitzpatrick; Chongyuan Luo; Joseph R. Nery; Michael Nunn; Angeline C. Rivkin; Wei Tian; Bertha Dominguez; Tony Ito-Cole; Matthew Jacobs; Xin Jin; Cheng-Ta Lee; Kuo-Fen Lee; Paula Assakura Miyazaki; Yan Pang; Mohammad Rashid; Jared B. Smith; Minh Vu; Elora Williams; Tommaso Biancalani; A. Sina Booeshaghi; Megan Crow; Sandrine Dudoit; Stephan Fischer; Jesse Gillis; Qiwen Hu; Peter V. Kharchenko; Sheng-Yong Niu; Vasilis Ntranos; Elizabeth Purdom; Davide Risso; Hector Roux de Bézieux; Saroja Somasundaram; Kelly Street; Valentine Svensson; Eeshit Dhaval Vaishnav; Koen Van den Berge; Joshua D. Welch; Xu An; Helen S. Bateup; Ian Bowman; Rebecca K. Chance; Nicholas N. Foster; William Galbavy; Hui Gong; Lin Gou; Joshua T. Hatfield; Houri Hintiryan; Karla E. Hirokawa; Gukhan Kim; Daniel J. Kramer; Anan Li; Xiangning Li; Qingming Luo; Rodrigo Muñoz-Castañeda; David A. Stafford; Zhao Feng; Xueyan Jia; Shengdian Jiang; Tao Jiang; Xiuli Kuang; Rachael Larsen; Phil Lesnar; Yaoyao Li; Yuanyuan Li; Lijuan Liu; Hanchuan Peng; Lei Qu; Miao Ren; Zongcai Ruan; Elise Shen; Yuanyuan Song; Wayne Wakeman; Peng Wang; Yimin Wang; Yun Wang; Lulu Yin; Jing Yuan; Sujun Zhao; Xuan Zhao; Arun Narasimhan; Ramesh Palaniswamy; Samik Banerjee; Liya Ding; Dhananjay Huilgol; Bingxing Huo; Hsien-Chi Kuo; Sophie Laturnus; Xu Li; Partha P. Mitra; Judith Mizrachi; Quanxin Wang; Peng Xie; Feng Xiong; Yang Yu; Stephen W. Eichhorn; Jim Berg; Matteo Bernabucci; Yves Bernaerts; Cathryn René Cadwell; Jesus Ramon Castro; Rachel Dalley; Leonard Hartmanis; Gregory D. Horwitz; Xiaolong Jiang; Andrew L. Ko; Elanine Miranda; Shalaka Mulherkar; Philip R. Nicovich; Scott F. Owen; Rickard Sandberg; Staci A. Sorensen; Zheng Huan Tan; Shona Allen; Dirk Hockemeyer; Angus Y. Lee; Matthew B. Veldman; Ricky S. Adkins; Seth A. Ament; Héctor Corrada Bravo; Robert Carter; Apaala Chatterjee; Carlo Colantuoni; Jonathan Crabtree; Heather Creasy; Victor Felix; Michelle Giglio; Brian R. Herb; Jayaram Kancherla; Anup Mahurkar; Carrie McCracken; Lance Nickel; Dustin Olley; Joshua Orvis; Michael Schor; Greg Hood; Benjamin Dichter; Michael Grauer; Brian Helba; Anita Bandrowski; Nikolaos Barkas; Benjamin Carlin; Florence D. D’Orazi; Kylee Degatano; Thomas H. Gillespie; Farzaneh Khajouei; Kishori Konwar; Carol Thompson; Kathleen Kelly; Stephanie Mok; Susan Sunkin; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;

<jats:title>Abstract</jats:title><jats:p>Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization<jats:sup>1–5</jats:sup>. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.</jats:p>

Palabras clave: Multidisciplinary.

Pp. 86-102

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

Zizhen YaoORCID; Hanqing Liu; Fangming Xie; Stephan Fischer; Ricky S. AdkinsORCID; Andrew I. AldridgeORCID; Seth A. AmentORCID; Anna Bartlett; M. Margarita BehrensORCID; Koen Van den Berge; Darren Bertagnolli; Hector Roux de BézieuxORCID; Tommaso BiancalaniORCID; A. Sina BooeshaghiORCID; Héctor Corrada Bravo; Tamara Casper; Carlo Colantuoni; Jonathan CrabtreeORCID; Heather CreasyORCID; Kirsten Crichton; Megan CrowORCID; Nick Dee; Elizabeth L. Dougherty; Wayne I. Doyle; Sandrine DudoitORCID; Rongxin Fang; Victor Felix; Olivia Fong; Michelle GiglioORCID; Jeff Goldy; Mike HawrylyczORCID; Brian R. Herb; Ronna Hertzano; Xiaomeng Hou; Qiwen Hu; Jayaram Kancherla; Matthew Kroll; Kanan Lathia; Yang Eric LiORCID; Jacinta D. Lucero; Chongyuan Luo; Anup MahurkarORCID; Delissa McMillen; Naeem M. Nadaf; Joseph R. NeryORCID; Thuc Nghi NguyenORCID; Sheng-Yong Niu; Vasilis Ntranos; Joshua Orvis; Julia K. OsteenORCID; Thanh PhamORCID; Antonio Pinto-DuarteORCID; Olivier Poirion; Sebastian PreisslORCID; Elizabeth PurdomORCID; Christine Rimorin; Davide Risso; Angeline C. Rivkin; Kimberly SmithORCID; Kelly Street; Josef Sulc; Valentine Svensson; Michael Tieu; Amy Torkelson; Herman TungORCID; Eeshit Dhaval VaishnavORCID; Charles R. Vanderburg; Cindy van VelthovenORCID; Xinxin WangORCID; Owen R. White; Z. Josh HuangORCID; Peter V. KharchenkoORCID; Lior Pachter; John Ngai; Aviv RegevORCID; Bosiljka TasicORCID; Joshua D. WelchORCID; Jesse Gillis; Evan Z. MacoskoORCID; Bing RenORCID; Joseph R. EckerORCID; Hongkui ZengORCID; Eran A. MukamelORCID

<jats:title>Abstract</jats:title><jats:p>Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain<jats:sup>1–3</jats:sup>. 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 regions<jats:sup>4</jats:sup>. 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.</jats:p>

Palabras clave: Multidisciplinary.

Pp. 103-110

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

Trygve E. BakkenORCID; Nikolas L. Jorstad; Qiwen Hu; Blue B. Lake; Wei Tian; Brian E. KalmbachORCID; Megan CrowORCID; Rebecca D. HodgeORCID; Fenna M. KrienenORCID; Staci A. Sorensen; Jeroen Eggermont; Zizhen YaoORCID; Brian D. Aevermann; Andrew I. AldridgeORCID; Anna Bartlett; Darren Bertagnolli; Tamara Casper; Rosa G. Castanon; Kirsten Crichton; Tanya L. Daigle; Rachel Dalley; Nick Dee; Nikolai DembrowORCID; Dinh Diep; Song-Lin Ding; Weixiu Dong; Rongxin Fang; Stephan Fischer; Melissa Goldman; Jeff Goldy; Lucas T. GraybuckORCID; Brian R. Herb; Xiaomeng Hou; Jayaram Kancherla; Matthew Kroll; Kanan Lathia; Baldur van LewORCID; Yang Eric LiORCID; Christine S. Liu; Hanqing Liu; Jacinta D. Lucero; Anup MahurkarORCID; Delissa McMillen; Jeremy A. MillerORCID; Marmar Moussa; Joseph R. NeryORCID; Philip R. Nicovich; Sheng-Yong Niu; Joshua Orvis; Julia K. OsteenORCID; Scott Owen; Carter R. Palmer; Thanh PhamORCID; Nongluk Plongthongkum; Olivier Poirion; Nora M. Reed; Christine Rimorin; Angeline Rivkin; William J. Romanow; Adriana E. Sedeño-Cortés; Kimberly Siletti; Saroja Somasundaram; Josef Sulc; Michael Tieu; Amy Torkelson; Herman TungORCID; Xinxin WangORCID; Fangming Xie; Anna Marie Yanny; Renee Zhang; Seth A. AmentORCID; M. Margarita BehrensORCID; Hector Corrada Bravo; Jerold ChunORCID; Alexander Dobin; Jesse Gillis; Ronna Hertzano; Patrick R. Hof; Thomas HölltORCID; Gregory D. HorwitzORCID; C. Dirk KeeneORCID; Peter V. KharchenkoORCID; Andrew L. Ko; Boudewijn P. LelieveldtORCID; Chongyuan Luo; Eran A. MukamelORCID; António Pinto-DuarteORCID; Sebastian PreisslORCID; Aviv RegevORCID; Bing RenORCID; Richard H. ScheuermannORCID; Kimberly SmithORCID; William J. Spain; Owen R. White; Christof KochORCID; Michael HawrylyczORCID; Bosiljka TasicORCID; Evan Z. MacoskoORCID; Steven A. McCarrollORCID; Jonathan T. Ting; Hongkui ZengORCID; Kun ZhangORCID; Guoping FengORCID; Joseph R. EckerORCID; Sten LinnarssonORCID; Ed S. LeinORCID

<jats:title>Abstract</jats:title><jats:p>The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals<jats:sup>1</jats:sup>. 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.</jats:p>

Palabras clave: Multidisciplinary.

Pp. 111-119

DNA methylation atlas of the mouse brain at single-cell resolution

Hanqing Liu; Jingtian ZhouORCID; Wei Tian; Chongyuan Luo; Anna Bartlett; Andrew AldridgeORCID; Jacinta Lucero; Julia K. Osteen; Joseph R. NeryORCID; Huaming Chen; Angeline Rivkin; Rosa G. Castanon; Ben Clock; Yang Eric LiORCID; Xiaomeng Hou; Olivier B. Poirion; Sebastian Preissl; Antonio Pinto-DuarteORCID; Carolyn O’Connor; Lara Boggeman; Conor Fitzpatrick; Michael Nunn; Eran A. MukamelORCID; Zhuzhu Zhang; Edward M. CallawayORCID; Bing RenORCID; Jesse R. DixonORCID; M. Margarita BehrensORCID; Joseph R. EckerORCID

<jats:title>Abstract</jats:title><jats:p>Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus DNA methylation sequencing<jats:sup>1,2</jats:sup> to profile 103,982 nuclei (including 95,815 neurons and 8,167 non-neuronal cells) from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas. We identified 161 cell clusters with distinct spatial locations and projection targets. We constructed taxonomies of these epigenetic types, annotated with signature genes, regulatory elements and transcription factors. These features indicate the potential regulatory landscape supporting the assignment of putative cell types and reveal repetitive usage of regulators in excitatory and inhibitory cells for determining subtypes. The DNA methylation landscape of excitatory neurons in the cortex and hippocampus varied continuously along spatial gradients. Using this deep dataset, we constructed an artificial neural network model that precisely predicts single neuron cell-type identity and brain area spatial location. Integration of high-resolution DNA methylomes with single-nucleus chromatin accessibility data<jats:sup>3</jats:sup> enabled prediction of high-confidence enhancer–gene interactions for all identified cell types, which were subsequently validated by cell-type-specific chromatin conformation capture experiments<jats:sup>4</jats:sup>. By combining multi-omic datasets (DNA methylation, chromatin contacts, and open chromatin) from single nuclei and annotating the regulatory genome of hundreds of cell types in the mouse brain, our DNA methylation atlas establishes the epigenetic basis for neuronal diversity and spatial organization throughout the mouse cerebrum.</jats:p>

Palabras clave: Multidisciplinary.

Pp. 120-128