Peng Zhouzhou, Lu Hui, Yang Qingwu, Xie Qi
Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China.
Front Aging Neurosci. 2022 May 19;14:885707. doi: 10.3389/fnagi.2022.885707. eCollection 2022.
Stroke is a major cause of morbidity and mortality worldwide. In the early stages of stroke, irreversible damage to neurons leads to high mortality and disability rates in patients. However, there are still no effective prevention and treatment measures for the resulting massive neuronal death in clinical practice. Astrocyte reprogramming has recently attracted much attention as an avenue for increasing neurons in mice after cerebral ischemia. However, the field of astrocyte reprogramming has recently been mired in controversy due to reports questioning whether newborn neurons are derived from astrocyte transformation. To better understand the process and controversies of astrocyte reprogramming, this review introduces the method of astrocyte reprogramming and its application in stroke. By targeting key transcription factors or microRNAs, astrocytes in the mouse brain could be reprogrammed into functional neurons. Additionally, we summarize some of the current controversies over the lack of cell lineage tracing and single-cell sequencing experiments to provide evidence of gene expression profile changes throughout the process of astrocyte reprogramming. Finally, we present recent advances in cell lineage tracing and single-cell sequencing, suggesting that it is possible to characterize the entire process of astrocyte reprogramming by combining these techniques.
中风是全球发病和死亡的主要原因。在中风的早期阶段,神经元的不可逆损伤导致患者的高死亡率和残疾率。然而,在临床实践中,对于由此导致的大量神经元死亡,仍然没有有效的预防和治疗措施。最近,星形胶质细胞重编程作为一种增加脑缺血后小鼠神经元数量的途径,受到了广泛关注。然而,由于有报道质疑新生神经元是否源自星形胶质细胞转化,星形胶质细胞重编程领域最近陷入了争议。为了更好地理解星形胶质细胞重编程的过程和争议,本综述介绍了星形胶质细胞重编程的方法及其在中风中的应用。通过靶向关键转录因子或微小RNA,小鼠大脑中的星形胶质细胞可以被重编程为功能性神经元。此外,我们总结了目前在缺乏细胞谱系追踪和单细胞测序实验方面的一些争议,以提供星形胶质细胞重编程全过程中基因表达谱变化的证据。最后,我们介绍了细胞谱系追踪和单细胞测序的最新进展,表明通过结合这些技术有可能描绘星形胶质细胞重编程的整个过程。