title: Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells.
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.
authors.affiliation: Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Schillerstrasse 46, D-80336 Munich, Germany.
authors.forename: Marisa
authors.initials: M
authors.lastname: Karow
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Sánchez
authors.forename: Christian
authors.initials: C
authors.lastname: Schichor
authors.forename: Giacomo
authors.initials: G
authors.lastname: Masserdotti
authors.forename: Felipe
authors.initials: F
authors.lastname: Ortega
authors.forename: Christophe
authors.initials: C
authors.lastname: Heinrich
authors.forename: Sergio
authors.initials: S
authors.lastname: Gascón
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Khan
authors.forename: D Chichung
authors.initials: DC
authors.lastname: Lie
authors.forename: Arianna
authors.initials: A
authors.lastname: Dellavalle
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Roland
authors.initials: R
authors.lastname: Goldbrunner
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
mesh_terms: D000200:Action Potentials; D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002540:Cerebral Cortex / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D009415:Nerve Net; D058953:Neural Stem Cells / Q000166:cytology*; D019636:Neurodegenerative Diseases / Q000628:therapy; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D020286:Pericytes / Q000166:cytology*; D012190:Retroviridae; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D033581:Stem Cell Transplantation; D009435:Synaptic Transmission
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055748:SOXB1 Transcription Factors; C065500:ASCL1 protein, human; C527782:SOX2 protein, human