Shared and distinct transcriptomic cell types across neocortical areas

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and...

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Published in:Nature (London) Vol. 563; no. 7729; pp. 72 - 78
Main Authors: Tasic, Bosiljka, Yao, Zizhen, Graybuck, Lucas T., Smith, Kimberly A., Nguyen, Thuc Nghi, Bertagnolli, Darren, Goldy, Jeff, Garren, Emma, Economo, Michael N., Viswanathan, Sarada, Penn, Osnat, Bakken, Trygve, Menon, Vilas, Miller, Jeremy, Fong, Olivia, Hirokawa, Karla E., Lathia, Kanan, Rimorin, Christine, Tieu, Michael, Larsen, Rachael, Casper, Tamara, Barkan, Eliza, Kroll, Matthew, Parry, Sheana, Shapovalova, Nadiya V., Hirschstein, Daniel, Pendergraft, Julie, Sullivan, Heather A., Kim, Tae Kyung, Szafer, Aaron, Dee, Nick, Groblewski, Peter, Wickersham, Ian, Cetin, Ali, Harris, Julie A., Levi, Boaz P., Sunkin, Susan M., Madisen, Linda, Daigle, Tanya L., Looger, Loren, Bernard, Amy, Phillips, John, Lein, Ed, Hawrylycz, Michael, Svoboda, Karel, Jones, Allan R., Koch, Christof, Zeng, Hongkui
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-11-2018
Nature Publishing Group
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Summary:The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex. Single-cell transcriptomics of more than 20,000 cells from two functionally distinct areas of the mouse neocortex identifies 133 transcriptomic types, and provides a foundation for understanding the diversity of cortical cell types.
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Author contributions H.Z. and K.S. conceptualized, and H.Z. and B.T designed and supervised the study. K.S. defined ALM coordinates based on loss-of-function experiments. K.A.S. managed the scRNA-seq pipeline. A.B. and J.Phillips managed pipeline establishment. D.B., J.G., K.L., C.R, M.T and TK.K. performed scRNA-seq. Z.Y, L.TG. and B.T analysed the data with contributions from O.F., O.P., TB., V.M., J.M., A.S. and M.H. I.W., H.A.S. and A.C. provided viral vectors. J.A.H., TN.N., K.E.H. and P.G. conducted viral tracing experiments. P.L., N.D., TC., S.P, E.B., M.K., N.V.S. and D.H. performed single-cell isolation. TN.N. and E.G. performed RNA ISH with RNAscope. L.M. and TL.D. generated transgenic mice. J. Pendergraft provided genotyping. R.L. provided mouse colony management. K.S., M.N.E., S.V. and L.L. provided manually collected cells from ALM. S.M.S. provided program management support. H.Z. and E.L. led the Cell Types Program at the Allen Institute. C.K. and A.R.J. provided funding, institutional support and management. L.TG., Z.Y, TN.N. and B.T prepared the figures. B.T. and H.Z. wrote the manuscript with contributions from C.K., K.S., L.TG., TN.N. and Z.Y., and in consultation with all authors.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-018-0654-5