Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.

Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocyte...

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Autores principales:	Russell C Addis, Fu-Chun Hsu, Rebecca L Wright, Marc A Dichter, Douglas A Coulter, John D Gearhart
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/364f29015cae470780f9ac0d200fe2db
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spelling	oai:doaj.org-article:364f29015cae470780f9ac0d200fe2db2021-11-18T07:32:36ZEfficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.1932-620310.1371/journal.pone.0028719https://doaj.org/article/364f29015cae470780f9ac0d200fe2db2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174877/?tool=EBIhttps://doaj.org/toc/1932-6203Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocytes, the most plentiful cells in the central nervous system, are an ideal starting population for the direct generation of dopaminergic neurons. In addition to their potential utility in cell replacement therapies for PD or in modeling the disease in vitro, astrocyte-derived dopaminergic neurons offer the prospect of direct in vivo reprogramming within the brain. As a first step toward this goal, we report the reprogramming of astrocytes to dopaminergic neurons using three transcription factors - ASCL1, LMX1B, and NURR1 - delivered in a single polycistronic lentiviral vector. The process is efficient, with 18.2±1.5% of cells expressing markers of dopaminergic neurons after two weeks. The neurons exhibit expression profiles and electrophysiological characteristics consistent with midbrain dopaminergic neurons, notably including spontaneous pacemaking activity, stimulated release of dopamine, and calcium oscillations. The present study is the first demonstration that a single vector can mediate reprogramming to dopaminergic neurons, and indicates that astrocytes are an ideal starting population for the direct generation of dopaminergic neurons.Russell C AddisFu-Chun HsuRebecca L WrightMarc A DichterDouglas A CoulterJohn D GearhartPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28719 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Russell C Addis Fu-Chun Hsu Rebecca L Wright Marc A Dichter Douglas A Coulter John D Gearhart Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
description	Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocytes, the most plentiful cells in the central nervous system, are an ideal starting population for the direct generation of dopaminergic neurons. In addition to their potential utility in cell replacement therapies for PD or in modeling the disease in vitro, astrocyte-derived dopaminergic neurons offer the prospect of direct in vivo reprogramming within the brain. As a first step toward this goal, we report the reprogramming of astrocytes to dopaminergic neurons using three transcription factors - ASCL1, LMX1B, and NURR1 - delivered in a single polycistronic lentiviral vector. The process is efficient, with 18.2±1.5% of cells expressing markers of dopaminergic neurons after two weeks. The neurons exhibit expression profiles and electrophysiological characteristics consistent with midbrain dopaminergic neurons, notably including spontaneous pacemaking activity, stimulated release of dopamine, and calcium oscillations. The present study is the first demonstration that a single vector can mediate reprogramming to dopaminergic neurons, and indicates that astrocytes are an ideal starting population for the direct generation of dopaminergic neurons.
format	article
author	Russell C Addis Fu-Chun Hsu Rebecca L Wright Marc A Dichter Douglas A Coulter John D Gearhart
author_facet	Russell C Addis Fu-Chun Hsu Rebecca L Wright Marc A Dichter Douglas A Coulter John D Gearhart
author_sort	Russell C Addis
title	Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
title_short	Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
title_full	Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
title_fullStr	Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
title_full_unstemmed	Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
title_sort	efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/364f29015cae470780f9ac0d200fe2db
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Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector.

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