Molecular Taxonomy and Evolution of the Primate dlPFC

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Abstract

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. Here, we assessed over 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. While most transcriptomically-defined cell subtypes are conserved, we detected several only in some species and 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 (SST) and tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, in certain interneurons, and also 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 dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

Citation

If you use the data in your research, please cite:

Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, 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 MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N. Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science. 2022 Sep 30;377(6614):eabo7257. doi: 10.1126/science.abo7257 . Epub 2022 Sep 30. PMID: 36007006; PMCID: PMC9614553.



Contact

Shaojie (Jay) Ma (j.ma@yale.edu); Sestan lab at Yale University



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Data Availability

The cross-species dlPFC snRNA-seq data (raw and processed) were deposited in the NeMO Archive under the identifier nemo:dat-zkgd0it

The raw data can also be downloaded from NeMO

The processed data can also be downloaded in: seurat format ; or tsv/mtx format: human , chimpanzee , rhesus , marmoset

The human dlPFC sn-multiome data can be downloaded from NCBI GEO under the accession number: GSE207334 . Additional fragment files can be downloaded from: aws

Code Availability

The scripts are deposited at Github: https://github.com/sestanlab/Cross-species-PFC-snRNA-seq

Alternative Data Visualization

The data can also be interactively visualized at: https://cellxgene.cziscience.com/collections/85624898-8006-4209-a84c-9a4d2591263a

Contact

Shaojie (Jay) Ma (j.ma@yale.edu); Sestan lab at Yale University