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Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons

Human embryonic stem cell (hESC)-derived dopamine neurons are currently moving toward clinical use for Parkinson’s disease (PD). However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown....

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Autores principales: Grealish, Shane, Heuer, Andreas, Cardoso, Tiago, Kirkeby, Agnete, Jönsson, Marie, Johansson, Jenny, Björklund, Anders, Jakobsson, Johan, Parmar, Malin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471831/
https://www.ncbi.nlm.nih.gov/pubmed/26004633
http://dx.doi.org/10.1016/j.stemcr.2015.04.011
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author Grealish, Shane
Heuer, Andreas
Cardoso, Tiago
Kirkeby, Agnete
Jönsson, Marie
Johansson, Jenny
Björklund, Anders
Jakobsson, Johan
Parmar, Malin
author_facet Grealish, Shane
Heuer, Andreas
Cardoso, Tiago
Kirkeby, Agnete
Jönsson, Marie
Johansson, Jenny
Björklund, Anders
Jakobsson, Johan
Parmar, Malin
author_sort Grealish, Shane
collection PubMed
description Human embryonic stem cell (hESC)-derived dopamine neurons are currently moving toward clinical use for Parkinson’s disease (PD). However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. In this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hESC-derived neurons in a rat model of PD and report that grafted human neurons integrate into the host neural circuitry in an unexpectedly rapid and extensive manner. The pattern of connectivity resembled that of local endogenous neurons, while ectopic connections were not detected. Revealing circuit integration of human dopamine neurons substantiates their potential use in clinical trials. Additionally, our data present rabies-based tracing as a valuable and widely applicable tool for analyzing graft connectivity that can easily be adapted to analyze connectivity of a variety of different neuronal sources and subtypes in different disease models.
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spelling pubmed-44718312015-06-22 Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons Grealish, Shane Heuer, Andreas Cardoso, Tiago Kirkeby, Agnete Jönsson, Marie Johansson, Jenny Björklund, Anders Jakobsson, Johan Parmar, Malin Stem Cell Reports Report Human embryonic stem cell (hESC)-derived dopamine neurons are currently moving toward clinical use for Parkinson’s disease (PD). However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. In this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hESC-derived neurons in a rat model of PD and report that grafted human neurons integrate into the host neural circuitry in an unexpectedly rapid and extensive manner. The pattern of connectivity resembled that of local endogenous neurons, while ectopic connections were not detected. Revealing circuit integration of human dopamine neurons substantiates their potential use in clinical trials. Additionally, our data present rabies-based tracing as a valuable and widely applicable tool for analyzing graft connectivity that can easily be adapted to analyze connectivity of a variety of different neuronal sources and subtypes in different disease models. Elsevier 2015-05-21 /pmc/articles/PMC4471831/ /pubmed/26004633 http://dx.doi.org/10.1016/j.stemcr.2015.04.011 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Report
Grealish, Shane
Heuer, Andreas
Cardoso, Tiago
Kirkeby, Agnete
Jönsson, Marie
Johansson, Jenny
Björklund, Anders
Jakobsson, Johan
Parmar, Malin
Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title_full Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title_fullStr Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title_full_unstemmed Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title_short Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
title_sort monosynaptic tracing using modified rabies virus reveals early and extensive circuit integration of human embryonic stem cell-derived neurons
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471831/
https://www.ncbi.nlm.nih.gov/pubmed/26004633
http://dx.doi.org/10.1016/j.stemcr.2015.04.011
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