Region-Restrict Astrocytes Exhibit Heterogeneous Susceptibility to Neuronal Reprogramming

• Published in: Stem cell reports Vol. 12; no. 2; pp. 290 - 304
• Main Authors: Hu, Xin, Qin, Shangyao, Huang, Xiao, Yuan, Yimin, Tan, Zijian, Gu, Yakun, Cheng, Xueyan, Wang, Dan, Lian, Xiao-Feng, He, Cheng, Su, Zhida
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.02.2019; Elsevier
• Subjects: Animals; ASCL1; astrocytes; Astrocytes - metabolism; Astrocytes - physiology; Cells, Cultured; Cellular Reprogramming - physiology; Central Nervous System - metabolism; Central Nervous System - physiology; heterogeneity; Mice; Mice, Inbred C57BL; neurons; Neurons - metabolism; Neurons - physiology; NGN2; Receptor, Notch1 - metabolism; reprogramming; Signal Transduction - physiology; Spinal Cord - metabolism; Spinal Cord - physiology; reprogramming; NGN2; astrocytes; ASCL1; neurons; heterogeneity
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2018.12.017

The adult CNS has poor ability to replace degenerated neurons following injury or disease. Recently, direct reprogramming of astrocytes into induced neurons has been proposed as an innovative strategy toward CNS repair. As a cell population that shows high diversity on physiological properties and functions depending on their spatiotemporal distribution, however, whether the astrocyte heterogeneity affect neuronal reprogramming is not clear. Here, we show that astrocytes derived from cortex, cerebellum, and spinal cord exhibit biological heterogeneity and possess distinct susceptibility to transcription factor-induced neuronal reprogramming. The heterogeneous expression level of NOTCH1 signaling in the different CNS regions-derived astrocytes is shown to be responsible for the neuronal reprogramming diversity. Taken together, our findings demonstrate that region-restricted astrocytes reveal different intrinsic limitation of the response to neuronal reprogramming. •Region-restrict astrocytes (ACs) exhibit obvious heterogeneity•Region-restrict ACs show distinct susceptibility to neuronal reprogramming•AC heterogeneity does not affect the maturation of induced neurons•Notch1 is involved in the neuronal reprogramming diversity of region-restrict ACs Su and colleagues show that astrocytes derived from cortex, cerebellum, and spinal cord exhibit biological heterogeneity and possess distinct susceptibility to transcription factor-induced neuronal reprogramming. The heterogeneous expression level of Notch1 signaling in the different CNS regions-derived astrocytes is shown to be responsible for the neuronal reprogramming diversity.