Charting the human-specific properties of gene expression networks in the infant prefrontal cortex

Abstract

Human infancy is characterized by protracted brain development coinciding with sensitive periods of extensive synaptic remodeling. Whether this is supported by human infant-specific transcriptional programs is unknown as comparative material in closely related primate species was unavailable. Here, we analyze rare newborn chimpanzee and age-matched human and rhesus macaque brain samples using single-cell transcriptomics and epigenomics. We identify a human infant-specific transcriptional program in immature oligodendrocytes that is overrepresented in autism risk genes and patient gene expression changes. Furthermore, a human infant-specific transcriptional program in the neural lineage is overrepresented in Parkinson's disease risk genes and patient gene expression changes. Both of these programs are part of a core transcriptional network that contains human-specific sequence changes in regulatory DNA and lacks cell lineage specificity. Our study provides insights into the stage-specific properties of human evolution during early infancy and sheds light on the human-specific propensities to neural disease.