Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons.
(2015) In Stem Cell Reports 4(6). p.975-983- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5442466
- author
- Grealish, Shane LU ; Heuer, Andreas LU ; Cardoso, Tiago LU ; Kirkeby, Agnete LU ; Jönsson, Marie LU ; Johansson, Jenny G LU ; Björklund, Anders LU ; Jakobsson, Johan LU and Parmar, Malin LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Stem Cell Reports
- volume
- 4
- issue
- 6
- pages
- 975 - 983
- publisher
- Cell Press
- external identifiers
-
- pmid:26004633
- wos:000356068100005
- scopus:84930928346
- pmid:26004633
- ISSN
- 2213-6711
- DOI
- 10.1016/j.stemcr.2015.04.011
- language
- English
- LU publication?
- yes
- id
- 59d68626-bd83-420d-8a4d-77c10a6670ef (old id 5442466)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26004633?dopt=Abstract
- date added to LUP
- 2016-04-01 14:18:13
- date last changed
- 2022-05-15 18:00:49
@article{59d68626-bd83-420d-8a4d-77c10a6670ef, abstract = {{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.}}, author = {{Grealish, Shane and Heuer, Andreas and Cardoso, Tiago and Kirkeby, Agnete and Jönsson, Marie and Johansson, Jenny G and Björklund, Anders and Jakobsson, Johan and Parmar, Malin}}, issn = {{2213-6711}}, language = {{eng}}, number = {{6}}, pages = {{975--983}}, publisher = {{Cell Press}}, series = {{Stem Cell Reports}}, title = {{Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons.}}, url = {{https://lup.lub.lu.se/search/files/3897932/8516348.pdf}}, doi = {{10.1016/j.stemcr.2015.04.011}}, volume = {{4}}, year = {{2015}}, }