Experimental Gerontology (Aug 2023)
MiR-210-5p promotes the differentiation of human induced pluripotent stem cells into dopaminergic neural precursors by targeting SMAD4 and SUFU and treats parkinsonian rats
Abstract
The differentiation of human induced pluripotent stem cells (hiPSCs) into functional dopaminergic neural precursors is the basis of cell therapy for Parkinson's disease (PD). However, the use of small molecule inhibitors/activators in the differentiation of hiPSCs in vitro leads to cell death and low differentiation efficiency. Moreover, the mechanism of differentiation remains unclear. MiR-210-5p was increased during hiPSCs differentiation. Whether it promotes hiPSCs differentiation and transplantation needs further study. Here, we overexpressed miR-210-5p in hiPSCs to study its roles and mechanisms. We found that miR-210-5p promoted the differentiation of hiPSCs into dopaminergic neural precursors and reduced the expression of SMAD4 and SUFU meanwhile. Luciferase assays showed that miR-210-5p binded to SMAD4 and SUFU, which are key molecules in the key signals (TGF-β and SHH) of hiPSCs differentiation. Furthermore, in the effect evaluation of cell transplantation into parkinsonian rats, the degree of behavioral recovery and the growth of transplanted cells in the group overexpressed miR-210-5p were similar to those in the positive group with all small molecule inhibitors/activators. Therefore, we conclude that miR-210-5p promotes the differentiation of hiPSCs into dopaminergic neural precursors by targeting SMAD4 and SUFU. In the therapeutic evaluation of cell transplantation, miR-210-5p can replace the use of corresponding small molecule inhibitors/activators to reduce cell death. This study provides an experimental basis and a new target for the miRNA-modified differentiation of hiPSCs and cell transplantation in clinical treatment of PD in the future.
