Abstract
We present a spatio-temporal assessment of microRNA (miRNA) 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 miRNAs and broad miRNA 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 transforming growth factor-beta 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.
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Acknowledgements
We thank the Allen Institute for Brain Science. This work was supported by the Intramural Research Program (IRP) of the National Institute of Child Health and Human Development, NIH. MNZ was also supported by the Baylor College of Medicine Medical Scientist Training Program (MSTP) and the NIH-Oxford/Cambridge Biomedical Scholars Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Ziats, M., Rennert, O. Identification of differentially expressed microRNAs across the developing human brain. Mol Psychiatry 19, 848–852 (2014). https://doi.org/10.1038/mp.2013.93
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DOI: https://doi.org/10.1038/mp.2013.93
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