To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

Allen Institute for Brain Science Seattle WA USA

Bar Ilan University Ramat Gan Israel

Baylor College of Medicine Houston TX USA

BrainScope Company Inc Bethesda MD USA

Cajal Institute Madrid Spain

CARTANA Stockholm Sweden

Centro de Biologia Molecular Severo Ochoa Madrid Spain

Charles University Prague Czech Republic

Christian Albrechts University Kiel Kiel Germany

Cold Spring Harbor Laboratory Laurel Hollow NY USA

Columbia University New York City NY USA

Department of Biomedicine Aarhus University Aarhus Denmark

Department of Genetics Harvard Medical School Boston MA USA

Department of Neurobiology Harvard Medical School Boston MA USA

Department of Neuroscience Carleton University Ottawa Ontario Canada

Department of Neuroscience University of Copenhagen Copenhagen Denmark

Department of Pathology University of California San Diego CA USA

Departments of Neurosurgery and of Neurology and Epileptology Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany

École Polytechnique Fédérale de Lausanne Lausanne Switzerland

European Molecular Biology Laboratory Hamburg Germany

European Molecular Biology Laboratory Heidelberg Germany

Friedrich Miescher Institute for Biological Research Basel Switzerland

George Mason University Fairfax VA USA

Harvard Medical School Cambridge MA USA

Harvard University Cambridge MA USA

Institute for Neuroanatomy University of Göttingen Göttingen Germany

J Craig Venter Institute La Jolla CA USA

Karolinska Institutet Stockholm Sweden

King's College London London UK

Krembil Research Institute Toronto Ontario Canada

Leiden University Medical Center Leiden the Netherlands

Macquarie University Sydney New South Wales Australia

Max Planck Institute for Biological Cybernetics Tübingen Germany

Max Planck Institute for Brain Research Frankfurt Germany

MSH Medical School Hamburg Germany

Research Centre for Natural Sciences Budapest Hungary

Research Centre Jülich Jülich Germany

Robarts Research Institute Western University London Ontario Canada

Ruhr University Bochum Bochum Germany

RWTH Aachen University Aachen Germany

Schulich School of Medicine and Dentistry Departments of Physiology Pharmacology and Psychiatry University of Western Ontario London Ontario Canada

Science for Life Laboratory Department of Biochemistry and Biophysics Stockholm University Solna Sweden

Scuola Normale Superior Pisa Italy

Sorbonne University Paris France

Stanford University Stanford CA USA

The University of Edinburgh Edinburgh UK

Univeristy of Rochester Rochester NY USA

Universidad Politécnica de Madrid Madrid Spain

University of Copenhagen Copenhagen Denmark

University of Haifa Haifa Israel

University of Oxford Oxford UK

University of Strathclyde Glasgow UK

University of Szeged Szeged Hungary

Vanderbilt University Nashville TN USA

Vrije Universiteit Amsterdam Amsterdam Netherlands

WM Keck Center for Collaborative Neuroscience Department of Cell Biology and Neuroscience Rutgers University New Brunswick Piscataway NJ USA

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Nat Neurosci. 2021 Apr;24(4):613. doi: 10.1038/s41593-020-00768-3. PubMed

Erratum v

Nat Neurosci. 2021 Apr;24(4):612. doi: 10.1038/s41593-020-00779-0. PubMed

Zobrazit více v PubMed

Magner, L.N. A History of the Life Sciences (Marcel Dekker, 1979).

Ramón y Cajal S. Rev Ciencias Méd. Barcelona. 1892;18:361–376.

Ramón y Cajal, S. Recuerdos de Mi Vida: Vol.2. Historia de Mi Labor Científica (Imprenta y librería de Nicolás Moya, 1917).

Ramón y Cajal, S. La Textura del Sistema Nerviosa del Hombre y los Vertebrados (Imprenta y librería de Nicolás Moya, 1904).

Hubel DH, Wiesel TN. Proc. R. Soc. Lond. B Biol. Sci. 1977;198:1–59. PubMed

Douglas RJ, Martin KAC, Whitteridge D. Neural Comput. 1989;1:480–488.

Mountcastle, V.B. Perceptual Neuroscience: The Cerebral Cortex (Harvard Univ. Press, 1998).

Lorente de Nó R. Trab. Lab. Invest. Bio. (Madrid) 1922;20:41–78.

Szentágothai J. Brain Res. 1975;95:475–496. PubMed

Peters, A. & Jones, E.G. Cerebral Cortex (Plenum, New York, 1984).

Lund JS. Annu. Rev. Neurosci. 1988;11:253–288. PubMed

Jones, E.G. & Diamond, I.T. (eds.). The Barrel Cortex of Rodents (Plenum, 1995).

Kozloski J, Hamzei-Sichani F, Yuste R. Science. 2001;293:868–872. PubMed

Cauli B, et al. J. Neurosci. 1997;17:3894–3906. PubMed PMC

Tsiola A, Hamzei-Sichani F, Peterlin Z, Yuste R. J. Comp. Neurol. 2003;461:415–428. PubMed

Guerra L, et al. Dev. Neurobiol. 2011;71:71–82. PubMed PMC

Ascoli GA, et al. Nat. Rev. Neurosci. 2008;9:557–568. PubMed PMC

Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B. Neurobiol. Aging. 2008;29:1754–1762. PubMed

DeFelipe J, et al. Nat. Rev. Neurosci. 2013;14:202–216. PubMed PMC

Shepherd GM, et al. Front. Neuroanat. 2019;13:25. PubMed PMC

Markram H, et al. Nat. Rev. Neurosci. 2004;5:793–807. PubMed

McGarry LM, et al. Front. Neural Circuits. 2010;4:12. PubMed PMC

Markram H, et al. Cell. 2015;163:456–492. PubMed

Butt SJB, et al. Neuron. 2005;48:591–604. PubMed

Kawaguchi Y, Kubota Y. Cereb. Cortex. 1997;7:476–486. PubMed

Yuste R. Neuron. 2005;48:524–527. PubMed

Kessaris N, Magno L, Rubin AN, Oliveira MG. Curr. Opin. Neurobiol. 2014;26:79–87. PubMed PMC

Fishell G, Kepecs A. Annu. Rev. Neurosci. 2019;43:1–30. PubMed PMC

Arendt D, et al. Nat. Rev. Genet. 2016;17:744–757. PubMed

Tosches MA, Laurent G. Curr. Opin. Neurobiol. 2019;56:199–208. PubMed

Dumitriu D, Cossart R, Huang J, Yuste R. Cereb. Cortex. 2007;17:81–91. PubMed

Jiang X, et al. Science. 2015;350:aac9462. PubMed PMC

Wheeler DW, et al. eLife. 2015;4:e09960. PubMed PMC

Mihaljević B, et al. BMC Bioinformatics. 2018;19:511. PubMed PMC

Shekhar K, et al. Cell. 2016;166:1308–1323.e30. PubMed PMC

Tasic B, et al. Nat. Neurosci. 2016;19:335–346. PubMed PMC

Paul A, et al. Cell. 2017;171:522–539.e20. PubMed PMC

Fishell G, Heintz N. Neuron. 2013;80:602–612. PubMed

Nelson SB, Sugino K, Hempel CM. Trends Neurosci. 2006;29:339–345. PubMed

Tasic B, et al. Nature. 2018;563:72–78. PubMed PMC

Yager TD, Nickerson DA, Hood LE. Trends Biochem. Sci. 1991;16:454. PubMed

Alivisatos AP, et al. Neuron. 2012;74:970–974. PubMed PMC

Bargmann CI, Newsome WT. JAMA Neurol. 2014;71:675–676. PubMed

Macosko EZ, et al. Cell. 2015;161:1202–1214. PubMed PMC

Klein AM, et al. Cell. 2015;161:1187–1201. PubMed PMC

Zheng GX, et al. Nat. Commun. 2017;8:14049. PubMed PMC

Habib N, et al. Nat. Methods. 2017;14:955–958. PubMed PMC

Bush EC, et al. Nat. Commun. 2017;8:105. PubMed PMC

Garber M, Grabherr MG, Guttman M, Trapnell C. Nat. Methods. 2011;8:469–477. PubMed

Stuart T, Satija R. Nat. Rev. Genet. 2019;20:257–272. PubMed

White JG, Southgate E, Thomson JN, Brenner S. Philos. Trans. R. Soc. Lond., B. 1986;314:1–340. PubMed

Ecker JR, et al. The BRAIN Initiative Cell Census Consortium. Neuron. 2017;96:542–557. PubMed PMC

Regev A, et al. eLife. 2017;6:e27041. PubMed

Lein E, Borm LE, Linnarsson S. Science. 2017;358:64–69. PubMed

Zeng H, Sanes JR. Nat. Rev. Neurosci. 2017;18:530–546. PubMed

Huang ZJ, Paul A. Nat. Rev. Neurosci. 2019;20:563–572. PubMed PMC

Fu M, Zuo Y. Trends Neurosci. 2011;34:177–187. PubMed PMC

Gerfen CR, Paletzki R, Heintz N. Neuron. 2013;80:1368–1383. PubMed PMC

He M, et al. Neuron. 2016;91:1228–1243. PubMed PMC

Roselli C, et al. Nat. Genet. 2018;50:1225–1233. PubMed PMC

Hodge RD, et al. Nature. 2019;573:61–68. PubMed PMC

Nowakowski TJ, et al. Science. 2017;358:1318–1323. PubMed PMC

Mayer C, et al. Nature. 2018;555:457–462. PubMed PMC

Mi D, et al. Science. 2018;360:81–85. PubMed PMC

Winnubst J, et al. Cell. 2019;179:268–281.e13. PubMed PMC

Sugino K, et al. Nat. Neurosci. 2006;9:99–107. PubMed

Anderson SA, Eisenstat DD, Shi L, Rubenstein JL. Science. 1997;278:474–476. PubMed

Tosches MA, et al. Science. 2018;360:881–888. PubMed

Peng YR, et al. Cell. 2019;176:1222–1237.e22. PubMed PMC

Martersteck EM, et al. Cell Rep. 2017;18:2058–2072. PubMed PMC

Häring M, et al. Nat. Neurosci. 2018;21:869–880. PubMed

Rosenberg AB, et al. Science. 2018;360:176–182. PubMed PMC

Harris KD, et al. PLoS Biol. 2018;16:e2006387. PubMed PMC

Zeisel A, et al. Science. 2015;347:1138–1142. PubMed

Boldog E, et al. Nat. Neurosci. 2018;21:1185–1195. PubMed PMC

Cadwell CR, et al. Nat. Biotechnol. 2016;34:199–203. PubMed PMC

Chen KH, Boettiger AN, Moffitt JR, Wang S, Zhuang X. Science. 2015;348:aaa6090. PubMed PMC

Durruthy-Durruthy R, et al. Cell. 2014;157:964–978. PubMed PMC

Trapnell C, et al. Nat. Biotechnol. 2014;32:381–386. PubMed PMC

Shalek AK, et al. Nature. 2014;510:363–369. PubMed PMC

Fiers MWEJ, et al. Brief. Funct. Genomics. 2018;17:246–254. PubMed PMC

Benavides-Piccione R, Hamzei-Sichani F, Ballesteros-Yáñez I, DeFelipe J, Yuste R. Cereb. Cortex. 2006;16:990–1001. PubMed

Hawrylycz MJ, et al. Nature. 2012;489:391–399. PubMed PMC

Bakken TE, et al. PLoS ONE. 2018;13:e0209648. PubMed PMC

Somogyi P. Brain Res. 1977;136:345–350. PubMed

Fairén A, Valverde F. J. Comp. Neurol. 1980;194:761–779. PubMed

Woodruff AR, et al. J. Neurosci. 2011;31:17872–17886. PubMed PMC

Cauli B, et al. Proc. Natl. Acad. Sci. USA. 2000;97:6144–6149. PubMed PMC

Krimer LS, et al. J. Neurophysiol. 2005;94:3009–3022. PubMed

Armañanzas R, Ascoli GA. Trends Neurosci. 2015;38:307–318. PubMed PMC

Andrews TS, Hemberg M. Mol. Aspects Med. 2018;59:114–122. PubMed

Kiselev VY, et al. Nat. Methods. 2017;14:483–486. PubMed PMC

Santana R, McGarry LM, Bielza C, Larrañaga P, Yuste R. Front. Neural Circuits. 2013;7:185. PubMed PMC

Liu L, Tang L, Dong W, Yao S, Zhou W. Springerplus. 2016;5:1608. PubMed PMC

van der Maaten L, Hinton G. J. Mach. Learn. Res. 2008;9:2579–2605.

Mansergh FC, Carrigan M, Hokamp K, Farrar GJ. Mol. Vis. 2015;21:61–87. PubMed PMC

Tang K, Ruozzi N, Belanger D, Jebara T. Bethe learning of graphical models via MAP decoding. Artificial Intelligence and Statistics (AISTATS). Proc. Mach. Learn. Res. 2016;51:1096–1104.

Sümbül U, Zlateski A, Vishwanathan A, Masland RH, Seung HS. Front. Neuroanat. 2014;8:139. PubMed PMC

Romesburg, H.C. Cluster Analysis for Researchers (Lifetime Learning, 1984).

Arendt D, Bertucci PY, Achim K, Musser JM. Curr. Opin. Neurobiol. 2019;56:144–152. PubMed PMC

Wiley, E.O. & Liberman, B.S. Phylogenetics: Theory and Practice of Phylogenetic Systematics (Wiley-Blackwell, 2011).

Siebert S, et al. Science. 2019;365:eaav9314. PubMed

Crow M, Paul A, Ballouz S, Huang ZJ, Gillis J. Nat. Commun. 2018;9:884. PubMed PMC

Bard J, Rhee SY, Ashburner M. Genome Biol. 2005;6:R21. PubMed PMC

Osumi-Sutherland D. BMC Bioinformatics. 2017;18:558. PubMed PMC

Masci AM, et al. BMC Bioinformatics. 2009;10:70. PubMed PMC

Smith B, et al. Nat. Biotechnol. 2007;25:1251–1255. PubMed PMC

Pereira P, Gama J, Pedroso J. IEEE Trans. Knowl. Data Eng. 2008;20:615–627.

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. J. Mol. Biol. 1990;215:403–410. PubMed

Bakken T, et al. BMC Bioinformatics. 2017;18:559. PubMed PMC

The evolution of brain structure captured in stereotyped cell count and cell type distributions