Identification of Differentially Expressed MicroRNAs Across the Developing Human Brain

We present a spatio-temporal assessment of microRNA expression throughout early human brain development. We assessed the prefrontal cortex, hippocampus, and cerebellum of 18 normal human donor brains spanning infancy through adolescence by RNA-seq. We discovered differentially expressed microRNAs and broad microRNA patterns across both temporal and spatial dimensions, and between male and female prefrontal cortex. Putative target genes of the differentially expressed miRNAs were identified, which demonstrated functional enrichment for transcription regulation, synaptogenesis, and other basic intracellular processes. Sex-biased miRNAs also targeted genes related to Wnt and TGF-β pathways. The differentially expressed miRNA targets were highly enriched for gene sets related to autism, schizophrenia, bipolar disorder, and depression, but not neurodegenerative diseases, epilepsy, or other adult-onset psychiatric diseases. Our results suggest critical roles for the identified miRNAs in transcriptional networks of the developing human brain and neurodevelopmental disorders.