Advanced

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

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 (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:
author
organization
publishing date
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
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
2015-06-05 13:08:41
date last changed
2017-10-22 04:18:14
@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          = {http://dx.doi.org/10.1016/j.stemcr.2015.04.011},
  volume       = {4},
  year         = {2015},
}