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.

Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells / M. Karow, R. Sánchez, C. Schichor, G. Masserdotti, F. Ortega, C. Heinrich, S. Gascón, M.A. Khan, D.C. Lie, A. Dellavalle, G. Cossu, R. Goldbrunner, M. Götz, B. Berninger. - In: CELL STEM CELL. - ISSN 1934-5909. - 11:4(2012 Oct 04), pp. 471-476. [10.1016/j.stem.2012.07.007]

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

M.A. Khan;G. Cossu;
2012

Abstract

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.
Neurogenesis; Nuclear Reprogramming; Action Potentials; Adult; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cells, Cultured; Cerebral Cortex; Humans; Induced Pluripotent Stem Cells; Mice; Nerve Net; Neural Stem Cells; Neurodegenerative Diseases; Neurons; Pericytes; Retroviridae; SOXB1 Transcription Factors; Stem Cell Transplantation; Synaptic Transmission
Settore BIO/17 - Istologia
4-ott-2012
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/233704
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