Role of mirna-mrna interaction in neural stem cell differentiation of induced pluripotent stem cells

Satish Kumar, Joanne E. Curran, Erica Deleon, Ana C. Leandro, Tom E. Howard, Donna M. Lehman, Sarah Williams-Blangero, David C. Glahn, John Blangero

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number6980
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Volume21
Issue number19
DOIs
StatePublished - Oct 1 2020

Keywords

  • Gene expression regulation
  • Human
  • Induced pluripotent stem cell
  • MRNA
  • MiRNA
  • Neural stem cell

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'Role of mirna-mrna interaction in neural stem cell differentiation of induced pluripotent stem cells'. Together they form a unique fingerprint.

  • Cite this

    Kumar, S., Curran, J. E., Deleon, E., Leandro, A. C., Howard, T. E., Lehman, D. M., Williams-Blangero, S., Glahn, D. C., & Blangero, J. (2020). Role of mirna-mrna interaction in neural stem cell differentiation of induced pluripotent stem cells. International journal of molecular sciences, 21(19), 1-15. [6980]. https://doi.org/10.3390/ijms21196980