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Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.

Authors
  • Shen, Yinan1
  • Liu, Feng2
  • Duan, Jiazhi2
  • Wang, Wenhan2
  • Yang, Hongru2
  • Wang, Zizhao1
  • Wang, Tailin3
  • Kong, Ying2
  • Ma, Baojin4
  • Hao, Min2
  • Zhao, Hang2
  • Liu, Hong2, 5
  • 1 Department of Physics & John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States. , (United States)
  • 2 State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China. , (China)
  • 3 Key Laboratory of Processing and Testing Technology of Glass & Functional Ceramics of Shandong Province, School of Materials, Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, China. , (China)
  • 4 Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, China. , (China)
  • 5 Institute for Advanced Interdisciplinary Research (IAIR), University of Jinan, Jinan, Shandong 250022, China. , (China)
Type
Published Article
Journal
Nano Letters
Publisher
American Chemical Society
Publication Date
Sep 08, 2021
Volume
21
Issue
17
Pages
7371–7378
Identifiers
DOI: 10.1021/acs.nanolett.1c02708
PMID: 34423634
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.

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