André Sousa, PhD – Slide of the Week

Title: Single-cell gene expression analysis reveals signatures of adult neurogenesis in mouse, pig and macaque, but not in humans.


A) Schematic of the analytic workflow. DG: dentate gyrus; CA: cornu ammonis; Sub: subiculum; EC: entorhinal cortex B) Seurat integration of all cells in the dentate gyrus (each dot represents one cell). RGL: radial glia-like cell; nIPC: neural intermediate progenitor cell; NB: neuroblast; Astro: astrocyte. C) Seurat integrations of astrocytes and granule cell lineage across species (each dot represents one cell). Arrow direction and length are correlated with cell differentiation path and speed, respectively.

Citation: Franjic D, Skarica M, Ma S, Tebbenkamp ATN, Arellano JI, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Liu Y, Spurrier J, Zhang L, Gudelj I, Jankovic-Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Neurogenic capacity and transcriptomic taxonomy of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 110, 1–18

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 im- plications 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.

About the Lab: Our lab aims to identify and characterize the molecular and cellular mechanisms that govern human brain development and evolution, and to apply that knowledge towards understanding neurodevelopmental and psychiatric disorders.

Investigator: André Sousa, PhD

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