André Sousa, PhD – Slide of the Week

André Sousa, PhD - Slide of the Week

Title: Taxonomy and divergent features of inhibitory neurons in the primate dorsolateral prefrontal cortex

Legend: (A) UMAP layout of all GABAergic inhibitory neuron subtypes with subclasses labeled. ChC, chandelier cells. (B) (Left) Sankey plots showing correspondence between predicted laminar organization and subtypes and/or subclasses. (Right) SST expression across putative cortical layers. Significance was tested with a one-sided Wilcoxon Rank Sum test (***, P < 0.001; ns, not significant). (C) colocalization of SST and RELN (arrowhead) in human dlPFC L1 revealed by double RNA in situ hybridization. Scale bar, 20 mm. (D) (Left) log-normalized expression of TH. (Middle) Double immunostaining for SST and TH. (Right) Proportion of SST+ and SST- cells within TH+ neurons. Scale bars, 20 mm in all species. (E) Immunofluorescence staining for TH and SST (left) or DDC (right), combined with SST RNA in situ hybridization. Scale bars, 20 mm. (F) Proportion of SST+ and SST− cells in human TH+ neurons.

Citation:  Ma S*, Skarica M*, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R,  Krsnik Z, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin M-R, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM#, Sousa AMM#, Sestan N#. (2022) Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 377, abo7257. (*co-first author; # corresponding author)

Abstract: The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

Andre Sousa, PhD
Andre Sousa, PhD

Investigator: André Sousa, PhD

About the Lab: The Sousa 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.

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