Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells

Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Schillerstrasse 46, D-80336 Munich, Germany.
Cell stem cell (Impact Factor: 22.27). 10/2012; 11(4):471-6. DOI: 10.1016/j.stem.2012.07.007
Source: PubMed


Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.

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Available from: Sergio Gascón, Sep 30, 2015
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    • "Overexpression of key transcription factors such as Neurogenein2, Mash1 or Sox2 can convert pericytes, astroglia or oligodendrocyte progenitor cells into functional neurons in situ (Heinrich et al., 2014; Heinrich et al., 2010; Karow et al., 2012). Such exciting technologies offer unprecedented potential to fundamentally reconfigure the structure and function of diseased brain regions. "
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    • "In this context, studies have defined sets of transcription factors that can directly reprogram somatic cells into another cell type without passing through the pluripotent state (Ginsberg et al., 2012; Ieda et al., 2010; Karow et al., 2012; Vierbuchen et al., 2010). Using a strategy of re-expressing key developmental regulators in vitro/in vivo, adult cell reprogramming occurs, through which induced cells residing in their native environment might promote their survival and/or maturation (Ginsberg et al., 2012; Ieda et al., 2010; Karow et al., 2012; Qian et al., 2012; Vierbuchen et al., 2010; Zhou et al., 2008). "
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