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A novel two-factor ...
A novel two-factor monosynaptic TRIO tracing method for assessment of circuit integration of hESC-derived dopamine transplants
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- Aldrin-Kirk, Patrick (author)
- Lund University,Lunds universitet,Human neural utvecklingsbiologi,Forskargrupper vid Lunds universitet,Human Neural Developmental Biology,Lund University Research Groups
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- Åkerblom, Malin (author)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Cardoso, Tiago (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Nolbrant, Sara (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Adler, Andrew F. (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Liu, Xiaohe (author)
- Lund University,Lunds universitet,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,Medical Microspectroscopy,Lund University Research Groups
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- Heuer, Andreas (author)
- Lund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups
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- Davidsson, Marcus (author)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Parmar, Malin (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Björklund, Tomas (author)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English 14 s.
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In: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 17:1, s. 159-172
- Related links:
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- AAV-MNM008
- animal model
- capcid engineering
- Cell replacement
- circuit mapping
- dopamine neurons
- human embryonic stem cells
- monosynaptic tracing
- Parkinson's disease
- retrograde transport
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Aldrin-Kirk, Pat ...
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Åkerblom, Malin
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Cardoso, Tiago
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Nolbrant, Sara
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Adler, Andrew F.
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Liu, Xiaohe
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show more...
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Heuer, Andreas
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Davidsson, Marcu ...
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Parmar, Malin
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Björklund, Tomas
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Stem Cell Report ...
- By the university
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Lund University