Direct reprogramming of human astrocytes into neural stem cells and neurons

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• 作者：Stefania Corti^a ; ^b ; Monica Nizzardo^a ; Chiara Simone^a ; Marianna Falcone^a ; Chiara Donadoni^a ; Sabrina Salani^a ; Federica Rizzo^a ; Martina Nardini^a ; Giulietta Riboldi^a ; Francesca Magri^a ; Chiara Zanetta^a ; Irene Faravelli^a ; Nereo Bresolin^a ; ^b ; ^c ; Giacomo P. Comi^a ; ^b ; ^{giacomo.comi@unimi.it}
• 关键词：ESC ; Embryonic Stem Cell ; iPSC ; induced Pluripotent Stem Cell ; NSC ; Neural Stem Cell
• 刊名：Experimental Cell Research
• 出版年：2012
• 期刊代码：292_00144827
• 类别：med
• 出版时间：1 August, 2012
• 卷：318
• 期：13
• 页码：1528-1541
• 文件大小：3563 K

摘要

Generating neural stem cells and neurons from reprogrammed human astrocytes is a potential strategy for neurological repair. Here we show dedifferentiation of human cortical astrocytes into the neural stem/progenitor phenotype to obtain progenitor and mature cells with a neural fate. Ectopic expression of the reprogramming factors OCT4, SOX2, or NANOG into astrocytes in specific cytokine/culture conditions activated the neural stem gene program and induced generation of cells expressing neural stem/precursor markers. Pure CD44 + mature astrocytes also exhibited this lineage commitment change and did not require passing through a pluripotent state. These astrocyte-derived neural stem cells gave rise to neurons, astrocytes, and oligodendrocytes and showed in vivo engraftment properties. ASCL1 expression further promoted neuronal phenotype acquisition in vitro and in vivo. Methylation analysis showed that epigenetic modifications underlie this process. The restoration of multipotency from human astrocytes has potential in cellular reprogramming of endogenous central nervous system cells in neurological disorders.