1. Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons
- Author
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Sergey L. Gratiy, Sara Kebede, Chris Hill, Clare Gamlin, Jeffrey G. Ojemann, Tom Egdorf, Ed S. Lein, Lydia Potekhina, Alice Mukora, Shea Ransford, Matthew Mallory, Tim S. Heistek, Jonathan T. Ting, Gábor Tamás, Philip C. De Witt Hamer, Rebecca de Frates, Medea McGraw, Gábor Molnár, Jim Berg, Szabina Furdan, Patrick R. Hof, Natalia A. Goriounova, David Feng, David Reid, Elliot R. Thomsen, Michael Tieu, Katelyn Ward, C. Dirk Keene, Florence D’Orazi, Mean Hwan Kim, Daniel Park, Amy Torkelson, Agata Budzillo, Katherine Baker, Michael Hawrylycz, Krissy Brouner, Andrew L. Ko, DiJon Hill, Kyla Berry, Peter Chong, Jessica Trinh, Desiree A. Marshall, Katherine E. Link, Brian Lee, Jasmine Bomben, Aaron Szafer, Gabe J. Murphy, Viktor Szemenyei, Madie Hupp, Lauren Alfiler, Nick Dee, Zizhen Yao, Luke Esposito, Tamara Casper, Erica J. Melief, Susan M. Sunkin, Lindsay Ng, Hongkui Zeng, Pál Barzó, Allison Beller, Lydia Ng, Charles Cobbs, Darren Bertagnolli, Kiet Ngo, Bosiljka Tasic, John W. Phillips, Christine Rimorin, Alex M. Henry, Aaron Oldre, Michelle Maxwell, Wayne Wakeman, Delissa McMillen, Amanda Gary, Tsega Desta, Nathan Hansen, Hong Gu, Julie Nyhus, Staci A. Sorensen, Gáspár Oláh, Thomas Chartrand, Kirsten Crichton, Matthew Kroll, Josef Sulc, Jeremy A. Miller, Amy Bernard, Lisa Kim, Herman Tung, Idan Segev, Kristen Hadley, David Sandman, Anoop P. Patel, Colin Farrell, Allan R. Jones, Lisa Keene, Sander Idema, Changkyu Lee, Stephanie Mok, Augustin Ruiz, Caitlin S. Latimer, Tim Jarsky, Kris Bickley, Anton Arkhipov, Ramkumar Rajanbabu, Thomas Braun, Costas A. Anastassiou, Anatoly Buchin, Nathan W. Gouwens, Philip R. Nicovich, Richard G. Ellenbogen, Olivia Fong, Grace Williams, Rachel Enstrom, Rachel A. Dalley, Daniel L. Silbergeld, Attila Ozsvár, Kimberly A. Smith, Ryder P. Gwinn, Songlin Ding, Rafael Yuste, Manuel Ferreira, Victoria Omstead, Samuel Dingman Lee, Norbert Mihut, Hanchuan Peng, Brian E. Kalmbach, Eliza Barkan, Melissa Gorham, Boaz P. Levi, Trygve E. Bakken, Jeff Goldy, Djai B. Heyer, Nadezhda Dotson, Rusty Mann, Rebecca D. Hodge, Christof Koch, René Wilbers, Leona Mezei, Eline J. Mertens, Jae-Geun Yoon, Anna A. Galakhova, Christina A. Pom, Trangthanh Pham, Alexandra Glandon, Christiaan P. J. de Kock, Lucas T. Graybuck, and Huibert D. Mansvelder
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0303 health sciences ,Cell type ,Neocortex ,Neurofilament ,Biology ,Transcriptome ,03 medical and health sciences ,Glutamatergic ,0302 clinical medicine ,medicine.anatomical_structure ,Cortex (anatomy) ,Specialization (functional) ,medicine ,Neuroscience ,030217 neurology & neurosurgery ,Function (biology) ,030304 developmental biology - Abstract
The neocortex is disproportionately expanded in human compared to mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers that selectively make connections within the cortex and other telencephalic structures. Single-cell transcriptomic analyses of human and mouse cortex show an increased diversity of glutamatergic neuron types in supragranular cortex in human and pronounced gradients as a function of cortical depth. To probe the functional and anatomical correlates of this transcriptomic diversity, we describe a robust Patch-seq platform using neurosurgically-resected human tissues. We characterize the morphological and physiological properties of five transcriptomically defined human glutamatergic supragranular neuron types. Three of these types have properties that are specialized compared to the more homogeneous properties of transcriptomically defined homologous mouse neuron types. The two remaining supragranular neuron types, located exclusively in deep layer 3, do not have clear mouse homologues in supragranular cortex but are transcriptionally most similar to deep layer mouse intratelencephalic-projecting neuron types. Furthermore, we reveal the transcriptomic types in deep layer 3 that express high levels of non-phosphorylated heavy chain neurofilament protein that label long-range neurons known to be selectively depleted in Alzheimer’s disease. Together, these results demonstrate the power of transcriptomic cell type classification, provide a mechanistic underpinning for increased complexity of cortical function in human cortical evolution, and implicate discrete transcriptomic cell types as selectively vulnerable in disease.
- Published
- 2020
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