André Sousa, PhD – Slide of the Week

André Sousa, PhD - Slide of the Week

Title: Gene expression divergence between human and macaque brain throughout development

Legend: Interspecies divergence, measured as absolute difference in gene expression, between humans and macaques in sixteen brain regions throughout development reveals an hourglass pattern. The upper-quartile divergence among all genes is plotted. The gray planes represent the transition from prenatal to early postnatal development (late fetal transition, left) and from adolescence to adulthood (right). The highest divergence can be observed during early prenatal development in the prefrontal cortex (PFC). The lowest divergence can be observed perinatally and during adolescence.

Citation: Zhu Y*, Sousa AMM*, Gao T*, Skarica M*, Li M*, Santpere G, Esteller-Cucala P, Juan D, Ferrandez-Peral L, Golden FO, Yang M, Miller DJ, Marques-Bonet T, Kawasawa YI, Zhao H, Sestan N. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science 362, eaat8077

Abstract: Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the  pathogenesis of neuropsychiatric disorders.

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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