A novel two-factor monosynaptic TRIO tracing method for assessment of circuit integration of hESC-derived dopamine transplants.

Autor:	Aldrin-Kirk P; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Åkerblom M; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Cardoso T; Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Nolbrant S; Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Adler AF; Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Liu X; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Heuer A; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Davidsson M; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Parmar M; Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden., Björklund T; Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden. Electronic address: tomas.bjorklund@med.lu.se.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2022 Jan 11; Vol. 17 (1), pp. 159-172. Date of Electronic Publication: 2021 Dec 30.
DOI:	10.1016/j.stemcr.2021.11.014
Abstrakt:	Transplantation in Parkinson's disease using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons is a promising future treatment option. However, many of the mechanisms that govern their differentiation, maturation, and integration into the host circuitry remain elusive. Here, we engrafted hESCs differentiated toward a ventral midbrain DA phenotype into the midbrain of a preclinical rodent model of Parkinson's disease. We then injected a novel DA-neurotropic retrograde MNM008 adeno-associated virus vector capsid, into specific DA target regions to generate starter cells based on their axonal projections. Using monosynaptic rabies-based tracing, we demonstrated for the first time that grafted hESC-derived DA neurons receive distinctly different afferent inputs depending on their projections. The similarities to the host DA system suggest a previously unknown directed circuit integration. By evaluating the differential host-to-graft connectivity based on projection patterns, this novel approach offers a tool to answer outstanding questions regarding the integration of grafted hESC-derived DA neurons. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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