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Neuron. 2021 Nov 18; doi: 10.1016/j.neuron.2021.10.036. Epub 2021 Nov 18.

Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells.

Neuron

Daniel Franjic, Mario Skarica, Shaojie Ma, Jon I Arellano, Andrew T N Tebbenkamp, Jinmyung Choi, Chuan Xu, Qian Li, Yury M Morozov, David Andrijevic, Zvonimir Vrselja, Ana Spajic, Gabriel Santpere, Mingfeng Li, Shupei Zhang, Yang Liu, Joshua Spurrier, Le Zhang, Ivan Gudelj, Lucija Rapan, Hideyuki Takahashi, Anita Huttner, Rong Fan, Stephen M Strittmatter, Andre M M Sousa, Pasko Rakic, Nenad Sestan

Affiliations

  1. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
  2. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
  3. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Neurogenomics Group, Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), DCEXS, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain.
  4. Department of Biomedical Engineering, Yale Stem Cell Center and Yale Cancer Center, and Human and Translational Immunology Program, Yale University, New Haven, CT 06520, USA.
  5. Program in Cellular Neuroscience, Neurodegeneration and Repair, Departments of Neurology and of Neuroscience, Yale School of Medicine, New Haven, CT 06536, USA.
  6. Department of Pathology, Brady Memorial Laboratory, Yale School of Medicine, New Haven, CT 06510, USA.
  7. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Waisman Center and Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
  8. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
  9. Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Departments of Psychiatry and Comparative Medicine, Program in Cellular Neuroscience, Neurodegeneration and Repair, and Yale Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: [email protected].

PMID: 34798047 DOI: 10.1016/j.neuron.2021.10.036

Abstract

The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate neurogenic potential and cellular diversity, we profiled single-nucleus transcriptomes in five hippocampal-entorhinal subregions in humans, macaques, and pigs. Integrated cross-species analysis revealed robust transcriptomic and histologic signatures of neurogenesis in the adult mouse, pig, and macaque but not humans. Doublecortin (DCX), a widely accepted marker of newly generated granule cells, was detected in diverse human neurons, but it did not define immature neuron populations. To explore species differences in cellular diversity and implications for disease, we characterized subregion-specific, transcriptomically defined cell types and transitional changes from the three-layered archicortex to the six-layered neocortex. Notably, METTL7B defined subregion-specific excitatory neurons and astrocytes in primates, associated with endoplasmic reticulum and lipid droplet proteins, including Alzheimer's disease-related proteins. This resource reveals cell-type- and species-specific properties shaping hippocampal-entorhinal neurogenesis and function.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Alzheimer’s disease; METTL7B; adult neurogenesis; doublecortin; entorhinal cortex; evolution; hippocampus; immature neurons; neuroblast; single-cell RNA-seq

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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