Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy

Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity....

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Main Authors: Julio C. Aguila, Eva Hedlund, Rosario Sanchez-Pernaute
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2012/412040
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author Julio C. Aguila
Eva Hedlund
Rosario Sanchez-Pernaute
author_facet Julio C. Aguila
Eva Hedlund
Rosario Sanchez-Pernaute
author_sort Julio C. Aguila
collection DOAJ
description Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.
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spelling doaj-art-183bc62b28a64e9196f5ceb8a2f834f92025-02-03T06:15:11ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/412040412040Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell TherapyJulio C. Aguila0Eva Hedlund1Rosario Sanchez-Pernaute2Laboratory of Stem Cells and Neural Repair, Fundacion Inbiomed, Paseo Mikeletegi 81, 20009 San Sebastian, SpainDepartment of Neuroscience, Karolinska Institutet, Retzius Road 8, 17177 Stockholm, SwedenLaboratory of Stem Cells and Neural Repair, Fundacion Inbiomed, Paseo Mikeletegi 81, 20009 San Sebastian, SpainPluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.http://dx.doi.org/10.1155/2012/412040
spellingShingle Julio C. Aguila
Eva Hedlund
Rosario Sanchez-Pernaute
Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
Stem Cells International
title Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
title_full Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
title_fullStr Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
title_full_unstemmed Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
title_short Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy
title_sort cellular programming and reprogramming sculpting cell fate for the production of dopamine neurons for cell therapy
url http://dx.doi.org/10.1155/2012/412040
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