RT Journal Article SR Electronic T1 Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.31.018820 DO 10.1101/2020.03.31.018820 A1 Jim Berg A1 Staci A. Sorensen A1 Jonathan T. Ting A1 Jeremy A. Miller A1 Thomas Chartrand A1 Anatoly Buchin A1 Trygve E. Bakken A1 Agata Budzillo A1 Nick Dee A1 Song-Lin Ding A1 Nathan W. Gouwens A1 Rebecca D. Hodge A1 Brian Kalmbach A1 Changkyu Lee A1 Brian R. Lee A1 Lauren Alfiler A1 Katherine Baker A1 Eliza Barkan A1 Allison Beller A1 Kyla Berry A1 Darren Bertagnolli A1 Kris Bickley A1 Jasmine Bomben A1 Thomas Braun A1 Krissy Brouner A1 Tamara Casper A1 Peter Chong A1 Kirsten Crichton A1 Rachel Dalley A1 Rebecca de Frates A1 Tsega Desta A1 Samuel Dingman Lee A1 Florence D’Orazi A1 Nadezhda Dotson A1 Tom Egdorf A1 Rachel Enstrom A1 Colin Farrell A1 David Feng A1 Olivia Fong A1 Szabina Furdan A1 Anna A. Galakhova A1 Clare Gamlin A1 Amanda Gary A1 Alexandra Glandon A1 Jeff Goldy A1 Melissa Gorham A1 Natalia A. Goriounova A1 Sergey Gratiy A1 Lucas Graybuck A1 Hong Gu A1 Kristen Hadley A1 Nathan Hansen A1 Tim S. Heistek A1 Alex M. Henry A1 Djai B. Heyer A1 DiJon Hill A1 Chris Hill A1 Madie Hupp A1 Tim Jarsky A1 Sara Kebede A1 Lisa Keene A1 Lisa Kim A1 Mean-Hwan Kim A1 Matthew Kroll A1 Caitlin Latimer A1 Boaz P. Levi A1 Katherine E. Link A1 Matthew Mallory A1 Rusty Mann A1 Desiree Marshall A1 Michelle Maxwell A1 Medea McGraw A1 Delissa McMillen A1 Erica Melief A1 Eline J. Mertens A1 Leona Mezei A1 Norbert Mihut A1 Stephanie Mok A1 Gabor Molnar A1 Alice Mukora A1 Lindsay Ng A1 Kiet Ngo A1 Philip R. Nicovich A1 Julie Nyhus A1 Gaspar Olah A1 Aaron Oldre A1 Victoria Omstead A1 Attila Ozsvar A1 Daniel Park A1 Hanchuan Peng A1 Trangthanh Pham A1 Christina A. Pom A1 Lydia Potekhina A1 Ramkumar Rajanbabu A1 Shea Ransford A1 David Reid A1 Christine Rimorin A1 Augustin Ruiz A1 David Sandman A1 Josef Sulc A1 Susan M. Sunkin A1 Aaron Szafer A1 Viktor Szemenyei A1 Elliot R. Thomsen A1 Michael Tieu A1 Amy Torkelson A1 Jessica Trinh A1 Herman Tung A1 Wayne Wakeman A1 Katelyn Ward A1 René Wilbers A1 Grace Williams A1 Zizhen Yao A1 Jae-Geun Yoon A1 Costas Anastassiou A1 Anton Arkhipov A1 Pal Barzo A1 Amy Bernard A1 Charles Cobbs A1 Philip C. de Witt Hamer A1 Richard G. Ellenbogen A1 Luke Esposito A1 Manuel Ferreira A1 Ryder P. Gwinn A1 Michael J. Hawrylycz A1 Patrick R. Hof A1 Sander Idema A1 Allan R. Jones A1 C.Dirk Keene A1 Andrew L. Ko A1 Gabe J. Murphy A1 Lydia Ng A1 Jeffrey G. Ojemann A1 Anoop P. Patel A1 John W. Phillips A1 Daniel L. Silbergeld A1 Kimberly Smith A1 Bosiljka Tasic A1 Rafael Yuste A1 Idan Segev A1 Christiaan P.J. de Kock A1 Huibert D. Mansvelder A1 Gabor Tamas A1 Hongkui Zeng A1 Christof Koch A1 Ed S. Lein YR 2020 UL http://biorxiv.org/content/early/2020/04/02/2020.03.31.018820.abstract AB 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.