RT Journal Article SR Electronic T1 Single-cell RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates and humans JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.05.367482 DO 10.1101/2020.11.05.367482 A1 Trygve E. Bakken A1 Cindy T.J. van Velthoven A1 Vilas Menon A1 Rebecca D. Hodge A1 Zizhen Yao A1 Thuc Nghi Nguyen A1 Lucas T. Graybuck A1 Gregory D. Horwitz A1 Darren Bertagnolli A1 Jeff Goldy A1 Emma Garren A1 Sheana Parry A1 Tamara Casper A1 Soraya I. Shehata A1 Eliza R. Barkan A1 Aaron Szafer A1 Boaz P. Levi A1 Nick Dee A1 Kimberly A. Smith A1 Susan M. Sunkin A1 Amy Bernard A1 John W. Phillips A1 Michael Hawrylycz A1 Christof Koch A1 Gabe Murphy A1 Ed Lein A1 Hongkui Zeng A1 Bosiljka Tasic YR 2020 UL http://biorxiv.org/content/early/2020/11/12/2020.11.05.367482.abstract AB Abundant anatomical and physiological evidence supports the presence of at least three distinct types of relay glutamatergic neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex. Relay neuron diversity has also been described in the mouse dLGN (also known as LGd). Different types of relay neurons in mice, humans and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to other cellular properties and differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of relay neurons in the primate dLGN, magnocellular neurons, parvocellular neurons, and two cell types expressing canonical marker genes for koniocellular neurons. Surprisingly, despite extensive documented morphological and physiological differences between magno- and parvocellular neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. We also detected strong donor-specific gene expression signatures in both macaque and human relay neurons. Likewise, the dominant feature of relay neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to striking differences in morphology and cortical projection targets. Finally, we align cellular expression profiles across species and find homologous types of relay neurons in macaque and human, and distinct relay neurons in mouse.Competing Interest StatementThe authors have declared no competing interest.