Upregulation of Ngn1 by THBS4 Affects Neuronal Differentiation of NG2 Cells In Vitro
YANG Haijie*, FU Qiran, LEI Bingbing, YUAN Xin, SHANG Sinan, FENG Zhiwei*
As the fourth type of glial cell population in central nervous system, neuron-glial antigen 2 (NG2)-positive cells have the potential to differentiate into neurons and provide a potential source of cells for the regenerative treatment of neural injuries. However, the specific mechanism underlying neuronal transdifferentiation of NG2 cells is still unclear. In this study, we founded that thrombospondin 4 (THBS4) was involved in neuronal differentiation in NG2 cells. When THBS4 was overexpressed, the mRNA and protein expression levels of neuronal markers in NG2 cells were significantly up-regulated, such as Tuj1, MAP2, and NeuN. The expression of markers of glial cells was down-regulated, such as GFAP and Olig2. Conversely, when THBS4 was silenced, the expression pattern of these markers was just the opposite. Studies on transcription factors during NG2 cell differentiation indicated that THBS4-mediated NG2 cell differentiation may be associated with transcription factors Ngn1, ATF6, and Olig2. Our results suggest that THBS4 can promote the trans-differentiation of NG2 cells to neurons. It may support a theoretical basis for applying NG2 cells to the treatment of neurological diseases.
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