Molecular and cellular evolution of the primate dorsolateral prefrontal cortex

• Published in: Science (American Association for the Advancement of Science) Vol. 377; no. 6614; p. eabo7257
• Main Authors: Ma, Shaojie, Skarica, Mario, Li, Qian, Xu, Chuan, Risgaard, Ryan D, Tebbenkamp, Andrew T N, Mato-Blanco, Xoel, Kovner, Rothem, Krsnik, Željka, de Martin, Xabier, Luria, Victor, Martí-Pérez, Xavier, Liang, Dan, Karger, Amir, Schmidt, Danielle K, Gomez-Sanchez, Zachary, Qi, Cai, Gobeske, Kevin T, Pochareddy, Sirisha, Debnath, Ashwin, Hottman, Cade J, Spurrier, Joshua, Teo, Leon, Boghdadi, Anthony G, Homman-Ludiye, Jihane, Ely, John J, Daadi, Etienne W, Mi, Da, Daadi, Marcel, Marín, Oscar, Hof, Patrick R, Rasin, Mladen-Roko, Bourne, James, Sherwood, Chet C, Santpere, Gabriel, Girgenti, Matthew J, Strittmatter, Stephen M, Sousa, André M M, Sestan, Nenad
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 30.09.2022
• Subjects: Adult; Animals; Biological evolution; Biosynthesis; Brain; Catarrhini; Catecholamine; Catecholamines; Chimpanzees; Chromatin; Circuits; Clustering; Cognition; Divergence; Dopamine; Dopamine - metabolism; Dopamine receptors; Dorsolateral Prefrontal Cortex - cytology; Dorsolateral Prefrontal Cortex - metabolism; Entropy; Evolution; Evolution, Molecular; Foxp2 protein; Gene expression; Genes; Heterogeneity; Homology; Humans; Hydroxylase; Immunohistochemistry; Mental disorders; Microglia; Monkeys & apes; Neuronal-glial interactions; Neurons; Nuclei (cytology); Pan troglodytes; Phylogeny; Post-transcription; Prefrontal cortex; Primates; Primates - genetics; Regulatory mechanisms (biology); Regulatory sequences; Scientific Concepts; Sensory integration; Single-Cell Analysis; snRNA; Social behavior; Social interactions; Somatostatin - genetics; Somatostatin - metabolism; Specialization; Species; Species comparisons; Taxonomy; Transcriptome; Tyrosine; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Wildlife conservation
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abo7257

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 , 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.