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....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-06-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111500123X |
| _version_ | 1828241838037794816 |
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| author | Shane Grealish Andreas Heuer Tiago Cardoso Agnete Kirkeby Marie Jönsson Jenny Johansson Anders Björklund Johan Jakobsson Malin Parmar |
| author_facet | Shane Grealish Andreas Heuer Tiago Cardoso Agnete Kirkeby Marie Jönsson Jenny Johansson Anders Björklund Johan Jakobsson Malin Parmar |
| author_sort | Shane Grealish |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T22:06:50Z |
| format | Article |
| id | doaj.art-d1fe52c7ede24adf9d902ffe2fc73a53 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-12T22:06:50Z |
| publishDate | 2015-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-d1fe52c7ede24adf9d902ffe2fc73a532022-12-22T03:14:56ZengElsevierStem Cell Reports2213-67112015-06-014697598310.1016/j.stemcr.2015.04.011Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived NeuronsShane Grealish0Andreas Heuer1Tiago Cardoso2Agnete Kirkeby3Marie Jönsson4Jenny Johansson5Anders Björklund6Johan Jakobsson7Malin Parmar8Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Molecular Neurogenetics, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenLund Stem Cell Center, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, 22184 Lund, SwedenHuman 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.http://www.sciencedirect.com/science/article/pii/S221367111500123X |
| spellingShingle | Shane Grealish Andreas Heuer Tiago Cardoso Agnete Kirkeby Marie Jönsson Jenny Johansson Anders Björklund Johan Jakobsson Malin Parmar Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons Stem Cell Reports |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S221367111500123X |
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