Open Access

miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4

  • Authors:
    • Nianping Zhang
    • Ying Lyu
    • Xuebing Pan
    • Liping Xu
    • Aiguo Xuan
    • Xiaosong He
    • Wandan Huang
    • Dahong Long
  • View Affiliations

  • Published online on: July 11, 2017     https://doi.org/10.3892/ijmm.2017.3064
  • Pages: 814-824
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pluripotent stem cells (PSCs) are regarded as potential sources that provide specific neural cells for cell therapy in some nervous system diseases. However, the mechanisms underlying the neural differentiation of PSCs remain largely unknown. MicroRNAs (miRNAs or miRs) are a class of small non‑pro­tein-coding RNAs that act as critical regulatory molecules in many cellular processes. In this study, we found that miR‑146b‑5p expression was markedly increased following the neural induction of mouse embryonic stem cells (ESCs) or induced PSCs (iPSCs). In this study, to further identify the role of miR‑146b‑5p, we generated stable miR‑146b‑5p-overexpressing ESC and iPSC cell lines, and induced the differentiation of these cells by the adherent monolayer culture method. In the miR‑146b‑5p-overexpressing ESC- or iPSC-derived cultures, RT-qPCR analysis revealed that the mRNA expression levels of neuroectoderm markers, such as Sox1, Nestin and Pax6, were markedly increased, and flow cytometric analysis verified that the number of Nestin‑positive cells was higher in the miR‑146b‑5p-overexpressing compared with the control cells. Mechanistically, the miR‑146b‑5p-overexpressing ESCs or iPSCs exhibited a significant reduction in Oct4 expression, which may be an explanation for these cells having a tendency to differentiate towards the neural lineage. Moreover, we confirmed that miR‑146b‑5p directly targeted Smad4 and negatively regulated the transforming growth factor (TGF)-β signaling pathway, which contributed to the neural commitment of PSCs. Collectively, our findings uncover the essential role of miR‑146b‑5p in the neural conversion of PSCs.
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September-2017
Volume 40 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang N, Lyu Y, Pan X, Xu L, Xuan A, He X, Huang W and Long D: miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4. Int J Mol Med 40: 814-824, 2017.
APA
Zhang, N., Lyu, Y., Pan, X., Xu, L., Xuan, A., He, X. ... Long, D. (2017). miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4. International Journal of Molecular Medicine, 40, 814-824. https://doi.org/10.3892/ijmm.2017.3064
MLA
Zhang, N., Lyu, Y., Pan, X., Xu, L., Xuan, A., He, X., Huang, W., Long, D."miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4". International Journal of Molecular Medicine 40.3 (2017): 814-824.
Chicago
Zhang, N., Lyu, Y., Pan, X., Xu, L., Xuan, A., He, X., Huang, W., Long, D."miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4". International Journal of Molecular Medicine 40, no. 3 (2017): 814-824. https://doi.org/10.3892/ijmm.2017.3064