Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells

TY - JOUR

T1 - Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells

AU - Karow, Marisa

AU - Sanchez, Rodrigo

AU - Schichor, Christian

AU - Masserdotti, Giacomo

AU - Ortega, Felipe

AU - Heinrich, Christophe

AU - Gascon, Sergio

AU - Khan, Muhammad A

AU - Lie, D Chichung

AU - Dellavalle, Arianna

AU - Cossu, Giulio

AU - Goldbrunner, Roland

AU - Götz, Magdalena

AU - Berninger, Benedikt

PY - 2012/10/4

Y1 - 2012/10/4

N2 - 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.

AB - 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.

U2 - 10.1016/j.stem.2012.07.007

DO - 10.1016/j.stem.2012.07.007

M3 - Article

SN - 1934-5909

VL - 11

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 4

ER -