Human neocortical expansion involves glutamatergic neuron diversification
Jim Berg, Staci A. Sorensen, Jonathan T. Ting, Jeremy A. Miller, Thomas Chartrand, Anatoly Buchin, Trygve E. Bakken, Agata Budzillo, Nick Dee, Song‐Lin Ding, Nathan W. Gouwens, Rebecca D. Hodge, Brian Kalmbach, Changkyu Lee, Brian R. 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 L. 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 S. Latimer, Boaz P. Levi, Katherine E. Link, Matthew Mallory, Rusty Mann, Desiree A. Marshall, Michelle Maxwell, Mary McGraw, Delissa McMillen, Erica J. Melief, Eline J. Mertens, Leona Mezei, Norbert Mihut, Stephanie Mok, Gábor Molnár, Alice Mukora, Lindsay Ng, Kiet Ngo, Philip R. Nicovich, Julie Nyhus, Gáspár Oláh, Aaron Oldre, Victoria Omstead, Attila Ozsvár, Daniel Park, Hanchuan Peng, Trangthanh Pham, Christina Alice Pom, Lydia Potekhina, Ramkumar Rajanbabu, Shea Ransford, David Reid, Christine Rimorin, Augustin Ruiz, David Sandman, Josef Šulc
Abstract
Abstract The neocortex is disproportionately expanded in human compared with mouse 1,2 , both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth 3 . Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer’s disease 4,5 . Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.