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Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

By Jim Berg, Staci A. Sorensen, Jonathan T. Ting, Jeremy Miller, Tom Chartrand, Anatoly Buchin, Trygve E. Bakken, Agata Budzillo, Nick Dee, Song-Lin Ding, Nathan W. Gouwens, Rebecca D. Hodge, Brian E. Kalmbach, Changkyu Lee, Brian Lee, Lauren Alfiler, Katherine Baker, Eliza Barkan, Allison Beller, Kyla Berry, Darren Bertagnolli, Kris Bickley, Jasmine Bomben, Thomas Braun, Krissy Brouner, Tamara Casper, Peter Chong, Kirsten Crichton, Rachel Dalley, Rebecca de Frates, Tsega Desta, Samuel Dingman Lee, Florence D. D'Orazi, Nadezhda Dotson, Tom Egdorf, Rachel Enstrom, Colin Farrell, David Feng, Olivia Fong, Szabina Furdan, Anna A. Galakhova, Clare Gamlin, Amanda Gary, Alexandra Glandon, Jeff Goldy, Melissa Gorham, Natalia A. Goriounova, Sergey Gratiy, Lucas T. Graybuck, Hong Gu, Kristen Hadley, Nathan Hansen, Tim S. Heistek, Alex M. Henry, Djai B Heyer, DiJon Hill, Chris Hill, Madie Hupp, Tim Jarsky, Sara Kebede, Lisa Keene, Lisa Kim, Mean-Hwan Kim, Matthew Kroll, Caitlin Latimer, Boaz P. Levi, Katherine E. Link, Matthew Mallory, Rusty Mann, Desiree Marshall, Michelle Maxwell, Medea McGraw, Delissa McMillen, Erica Melief, Eline J. Mertens, Leona Mezei, Norbert Mihut, Stephanie Mok, Gabor Molnar, Alice Mukora, Lindsay Ng, Kiet Ngo, Philip R. Nicovich, Julie Nyhus, Gaspar Olah, Aaron Oldre, Victoria Omstead, Attila Ozsvar, Daniel Park, Hanchuan Peng, Thanh Pham, Christina A. Pom, Lydia Potekhina, Ramkumar Rajanbabu, Shea Ransford, David Reid, Christine Rimorin, Augustin Ruiz, David Sandman, Josef Sulc, Susan Sunkin, Aaron Szafer, Viktor Szemenyei, Elliot R. Thomsen, Michael Tieu, Amy Torkelson, Jessica Trinh, Herman Tung, Wayne Wakeman, Katelyn Ward, René Wilbers, Grace Williams, Zizhen Yao, Jae-Geun Yoon, Costas Anastassiou, Anton Arkhipov, Pal Barzo, Amy Bernard, Charles Cobbs, Philip C. de Witt Hamer, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Ryder P Gwinn, Mike Hawrylycz, Patrick R. Hof, Sander Idema, Allan R. Jones, C. Dirk Keene, Andrew L. Ko, Gabe Murphy, Lydia Ng, Jeffrey G Ojemann, Anoop P. Patel, John W. Phillips, Daniel L. Silbergeld, Kimberly Smith, Bosiljka Tasic, Rafael Yuste, Idan Segev, Christiaan P.J. de Kock, Huibert D. Mansvelder, Gabor Tamas, Hongkui Zeng, Christof Koch, Ed S. Lein

Posted 02 Apr 2020
bioRxiv DOI: 10.1101/2020.03.31.018820

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 labels 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.

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