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

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

Stem Cell Reports

Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, Lund University, Lund, Sweden. Electronic address:

Published: January 2022

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758947PMC
http://dx.doi.org/10.1016/j.stemcr.2021.11.014DOI Listing

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