Abstract
MicroRNAs (miRNA) play an essential role in the regulation of gene expression and influence signaling networks responsible for several cellular processes like differentiation of pluripotent stem cells. Despite several studies on the neurogenesis process, no global analysis of microRNA expression during differentiation of induced pluripotent stem cells (iPSC) to neuronal stem cells (NSC) has been done. Therefore, we compared the profile of microRNA expression in iPSC lines and in NSC lines derived from them, using microarray-based analysis. Two different protocols for NSC formation were used: Direct and two-step via neural rosette formation. We confirmed the new associations of previously described miRNAs in regulation of NSC differentiation from iPSC. We discovered upregulation of miR-10 family, miR-30 family and miR-9 family and downregulation of miR-302 and miR-515 family expression. Moreover, we showed that miR-10 family play a crucial role in the negative regulation of genes expression belonging to signaling pathways involved in neural differentiation: WNT signaling pathway, focal adhesion, and signaling pathways regulating pluripotency of stem cells.
Highlights
Stem cells, due to their pluripotent character and nearly unlimited potential to differentiate, are a useful tool in basic research, disease modeling, drug toxicity tests, and regenerative medicine
For the derivation of neuronal stem cells (NSC), we used one human induced pluripotent stem cell line, GPCCi001-A generated from primary human dermal fibroblasts according to previously established protocol [20] and one commercially available induced pluripotent stem cells (iPSC) cell line—iPSC cell line ND41658*H (Coriell Cell Repository, NY, USA)
As the induced pluripotent stem cells serves a great promise in regenerative medicine and therapies based on gene replacement or gene correction, especially in the field of neurodegenerative diseases, we believe that results presented in this study address the lack of the data concerning the molecular mechanisms underlying the neurogenesis process
Summary
Due to their pluripotent character and nearly unlimited potential to differentiate, are a useful tool in basic research, disease modeling, drug toxicity tests, and regenerative medicine. A turning point in stem cell research occurred with two seminal studies, which demonstrated that overexpression of four transcription factors (OSKM: OCT3/4, SOX2, KLF4 and c-MYC) induces pluripotency in adult murine [1] and human fibroblasts [2]. The use of induced pluripotent stem cells obviates the two critical issues of ESC cells: Graft rejection and ethical controversies. Differentiation of human induced pluripotent cells into neuronal cells is a potential source of neurons, astrocytes, and oligodendrocytes that can be used in regenerative medicine, to study the effects of drugs on the patient’s cells or to study the pathological mechanisms of diseases
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