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Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing

Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function...

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Detalles Bibliográficos
Autores principales: Fiorenzano, Alessandro, Sozzi, Edoardo, Parmar, Malin, Storm, Petter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226961/
https://www.ncbi.nlm.nih.gov/pubmed/34206038
http://dx.doi.org/10.3390/cells10061366
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author Fiorenzano, Alessandro
Sozzi, Edoardo
Parmar, Malin
Storm, Petter
author_facet Fiorenzano, Alessandro
Sozzi, Edoardo
Parmar, Malin
Storm, Petter
author_sort Fiorenzano, Alessandro
collection PubMed
description Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson’s disease (PD), whereas A10 neurons are largely unaffected by the condition, and their dysfunction is associated with neuropsychiatric disorders. Currently, DA neurons can only be reliably classified on the basis of topographical features, including anatomical location in the midbrain and projection targets in the forebrain. No systematic molecular classification at the genome-wide level has been proposed to date. Although many years of scientific efforts in embryonic and adult mouse brain have positioned us to better understand the complexity of DA neuron biology, many biological phenomena specific to humans are not amenable to being reproduced in animal models. The establishment of human cell-based systems combined with advanced computational single-cell transcriptomics holds great promise for decoding the mechanisms underlying maturation and diversification of human DA neurons, and linking their molecular heterogeneity to functions in the midbrain. Human pluripotent stem cells have emerged as a useful tool to recapitulate key molecular features of mature DA neuron subtypes. Here, we review some of the most recent advances and discuss the current challenges in using stem cells, to model human DA biology. We also describe how single cell RNA sequencing may provide key insights into the molecular programs driving DA progenitor specification into mature DA neuron subtypes. Exploiting the state-of-the-art approaches will lead to a better understanding of stem cell-derived DA neurons and their use in disease modeling and regenerative medicine.
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spelling pubmed-82269612021-06-26 Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing Fiorenzano, Alessandro Sozzi, Edoardo Parmar, Malin Storm, Petter Cells Review Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson’s disease (PD), whereas A10 neurons are largely unaffected by the condition, and their dysfunction is associated with neuropsychiatric disorders. Currently, DA neurons can only be reliably classified on the basis of topographical features, including anatomical location in the midbrain and projection targets in the forebrain. No systematic molecular classification at the genome-wide level has been proposed to date. Although many years of scientific efforts in embryonic and adult mouse brain have positioned us to better understand the complexity of DA neuron biology, many biological phenomena specific to humans are not amenable to being reproduced in animal models. The establishment of human cell-based systems combined with advanced computational single-cell transcriptomics holds great promise for decoding the mechanisms underlying maturation and diversification of human DA neurons, and linking their molecular heterogeneity to functions in the midbrain. Human pluripotent stem cells have emerged as a useful tool to recapitulate key molecular features of mature DA neuron subtypes. Here, we review some of the most recent advances and discuss the current challenges in using stem cells, to model human DA biology. We also describe how single cell RNA sequencing may provide key insights into the molecular programs driving DA progenitor specification into mature DA neuron subtypes. Exploiting the state-of-the-art approaches will lead to a better understanding of stem cell-derived DA neurons and their use in disease modeling and regenerative medicine. MDPI 2021-06-01 /pmc/articles/PMC8226961/ /pubmed/34206038 http://dx.doi.org/10.3390/cells10061366 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fiorenzano, Alessandro
Sozzi, Edoardo
Parmar, Malin
Storm, Petter
Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title_full Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title_fullStr Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title_full_unstemmed Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title_short Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing
title_sort dopamine neuron diversity: recent advances and current challenges in human stem cell models and single cell sequencing
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226961/
https://www.ncbi.nlm.nih.gov/pubmed/34206038
http://dx.doi.org/10.3390/cells10061366
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