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Molecular and Cellular Biochemistry

, Volume 395, Issue 1–2, pp 291–298 | Cite as

Inhibition of Notch signaling facilitates the differentiation of human-induced pluripotent stem cells into neural stem cells

  • Chun-Yuan Chen
  • Wei Liao
  • Yuan-Lei Lou
  • Qing Li
  • Bin Hu
  • Yang Wang
  • Zhi-Feng Deng
Article

Abstract

Neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) are becoming an appealing source of cell-based therapies of brain diseases. As such, it is important to understand the molecular mechanisms that regulate the differentiation of iPSCs toward NSCs. It is well known that Notch signaling governs the retention of stem cell features and drives stem cells fate. However, further studies are required to investigate the role of Notch signaling in the NSCs differentiation of iPSCs. In this study, we successfully generated NSCs from human iPSCs using serum-free medium supplemented with retinoic acid (RA) in vitro. We then assessed changes in the expression of Notch signaling-related molecules and some miRNAs (9, 34a, 200b), which exert their regulation by targeting Notch signaling. Moreover, we used a γ-secretase inhibitor (DAPT) to disturb Notch signaling. Data revealed that the levels of the Notch signaling-related molecules decreased, whereas those miRNAs increased, during this differentiation process. Inhibition of Notch signaling accelerated the formation of the neural rosette structures and the expression of NSC and mature neurocyte marker genes. This suggests that Notch signaling negatively regulated the neuralization of human iPSCs, and that this process may be regulated by some miRNAs.

Keywords

Induced pluripotent stem cell Neural stem cell Differentiation Notch signaling microRNA 

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No: 81160154, 81272170, 81060324), and the innovation team construction plan of Jiangxi Province (20113BCB24018).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Graduate School of Nanchang UniversityNanchangChina
  2. 2.Institute of UrologyThe First Affiliated Hospital of Nanchang UniversityNanchangChina
  3. 3.Institute of Orthopaedic SurgeryShanghai Jiaotong University Affiliated Sixth People’s HospitalShanghaiChina
  4. 4.Department of NeurosurgeryShanghai Jiaotong University Affiliated Sixth People’s HospitalShanghaiChina

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