Neonatal cortical astrocytes possess intrinsic potential in neuronal conversion in defined media

Peng Zeng1, Qiu-hong Hua1, Jun-yuan Gong1, Chang-jie Shi1, Xiao-ping Pi2, Xin Xie2, Ru Zhang1
1 Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
2 CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Correspondence to: Xin Xie:, Ru Zhang:,
DOI: 10.1038/s41401-020-00586-0
Received: 14 August 2020
Accepted: 19 November 2020
Advance online: 5 February 2021


Astrocytes are multifunctional brain cells responsible for maintaining the health and function of the central nervous system. Accumulating evidence suggests that astrocytes might be complementary source across different brain regions to supply new neurons during adult neurogenesis. In this study, we found that neonatal mouse cortical astrocytes can be directly converted into neurons when exposed to neurogenic differentiation culture conditions, with insulin being the most critical component. Detailed comparison studies between mouse cortical astrocytes and neuronal progenitor cells (NPCs) demonstrated the converted neuronal cells originate indeed from the astrocytes rather than NPCs. The neurons derived from mouse cortical astrocytes display typical neuronal morphologies, express neuronal markers and possess typical neuronal electrophysiological properties. More importantly, these neurons can survive and mature in the mouse brain in vivo. Finally, by comparing astrocytes from different brain regions, we found that only cortical astrocytes but not astrocytes from other brain regions such as hippocampus and cerebellum can be converted into neurons under the current condition. Altogether, our findings suggest that neonatal astrocytes from certain brain regions possess intrinsic potential to differentiate/transdifferentiate into neurons which may have clinical relevance in the future.
Keywords: cortical astrocytes; neonatal; neuronal conversion; insulin; heterogeneity

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