Ziats M N, Rennert O M
1] National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA [2] NIH-University of Cambridge Biomedical Scholars Program, Cambridge, UK [3] Baylor College of Medicine MSTP, Houston, TX, USA.
National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Mol Psychiatry. 2014 Jul;19(7):848-52. doi: 10.1038/mp.2013.93. Epub 2013 Aug 6.
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.
我们展示了对整个早期人类大脑发育过程中微小RNA（miRNA）表达的时空评估。我们通过RNA测序评估了18个从婴儿期到青春期的正常人类供体大脑的前额叶皮质、海马体和小脑。我们发现了在时间和空间维度上以及男性和女性前额叶皮质之间差异表达的miRNA和广泛的miRNA模式。确定了差异表达的miRNA的推定靶基因，这些基因在转录调控、突触形成和其他基本细胞内过程中显示出功能富集。性别偏向的miRNA也靶向与Wnt和转化生长因子-β途径相关的基因。差异表达的miRNA靶标在与自闭症、精神分裂症、双相情感障碍和抑郁症相关的基因集中高度富集，但在神经退行性疾病、癫痫或其他成人期精神疾病中未富集。我们的结果表明，所确定的miRNA在发育中的人类大脑转录网络和神经发育障碍中起关键作用。
