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  • Activation of a neural stem cell transcriptional program in parenchymal astrocytes.

Activation of a neural stem cell transcriptional program in parenchymal astrocytes.

eLife (2020-08-04)
Jens P Magnusson, Margherita Zamboni, Giuseppe Santopolo, Jeff E Mold, Mauricio Barrientos-Somarribas, Carlos Talavera-Lopez, Björn Andersson, Jonas Frisén
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.

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Sigma-Aldrich
牛血清白蛋白 来源于牛血清, lyophilized powder, BioReagent, suitable for cell culture
Sigma-Aldrich
表皮生长因子 来源于鼠颔下腺, EGF, suitable for cell culture
Sigma-Aldrich
杜氏磷酸盐缓冲盐水, Modified, with 36 mg sodium pyruvate, 50 mg streptomycin sulfate, 100 mg kanamycin monosulfate, 1000 mg glucose/L and CaCl2, liquid, 0.1 μm filtered, suitable for cell culture