Activation of a neural stem cell transcriptional program in parenchymal astrocytes

eLife

Jonas Frisén¹  Jeff E Mold¹  Mauricio Barrientos-Somarribas¹  Carlos Talavera-Lopez¹  Margherita Zamboni¹  Björn Andersson¹  Jens P Magnusson¹  Giuseppe Santopolo¹ 

[1] Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden;

关键词: neurogenesis;    astrocytes;    neural stem cells;    single-cell RNA sequencing;    regenerative medicine;   

DOI  :  10.7554/eLife.59733

来源: DOAJ

【 摘 要 】

Adult neural stem cells, located in discrete brain regions, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytes in vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells, progressing through a near-identical neurogenic program. Surprisingly, in the non-neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, these cortical astrocytes, and many striatal ones, stalled before entering transit-amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation.

【 授权许可】

Unknown