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.
CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Acta Pharmacol Sin. 2021 Nov;42(11):1757-1768. doi: 10.1038/s41401-020-00586-0. Epub 2021 Feb 5.
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.
星形胶质细胞是具有多种功能的脑细胞，负责维持中枢神经系统的健康和功能。越来越多的证据表明，星形胶质细胞可能是不同脑区之间补充神经元的来源，以在成年神经发生期间供应新的神经元。在这项研究中，我们发现，新生小鼠皮质星形胶质细胞在暴露于神经发生分化培养条件下时可以直接转化为神经元，其中胰岛素是最关键的成分。对小鼠皮质星形胶质细胞和神经祖细胞 (NPC) 之间的详细比较研究表明，转化而来的神经元确实源自星形胶质细胞而非 NPC。源自小鼠皮质星形胶质细胞的神经元具有典型的神经元形态，表达神经元标志物，并具有典型的神经元电生理特性。更重要的是，这些神经元可以在体内的小鼠脑中存活和成熟。最后，通过比较来自不同脑区的星形胶质细胞，我们发现只有皮质星形胶质细胞而不是来自其他脑区（如海马体和小脑）的星形胶质细胞可以在当前条件下转化为神经元。总之，我们的研究结果表明，来自特定脑区的新生星形胶质细胞具有内在的分化/转分化为神经元的潜力，这在未来可能具有临床意义。
