Role of miRNA-mRNA Interaction in Neural Stem Cell Differentiation of Induced Pluripotent Stem Cells

International Journal of Molecular Sciences

AnaC. Leandro¹  JoanneE. Curran¹  John Blangero¹  TomE. Howard¹  Satish Kumar²  Sarah Williams-Blangero²  Erica DeLeon²  DonnaM. Lehman³  DavidC. Glahn⁴ 

[1] Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA;Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, McAllen, TX 78504, USA;Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA;Department of Psychiatry, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA;

关键词: human;    induced pluripotent stem cell;    neural stem cell;    miRNA;    mRNA;    gene expression regulation;   

DOI  :  10.3390/ijms21196980

来源: DOAJ

【 摘 要 】

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10⁻¹⁵–1.44 × 10⁻⁴). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease.

【 授权许可】

Unknown