Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
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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.
In: Stem Cell Reports, Vol. 4, No. 6, 09.06.2015, p. 975-983.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons
AU - Grealish, Shane
AU - Heuer, Andreas
AU - Cardoso, Tiago
AU - Kirkeby, Agnete
AU - Jönsson, Marie
AU - Johansson, Jenny
AU - Björklund, Anders
AU - Jakobsson, Johan
AU - Parmar, Malin
PY - 2015/6/9
Y1 - 2015/6/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930928346&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2015.04.011
DO - 10.1016/j.stemcr.2015.04.011
M3 - Journal article
C2 - 26004633
AN - SCOPUS:84930928346
VL - 4
SP - 975
EP - 983
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 6
ER -
ID: 228506094