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Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

Lisa M. Smits, Stefano Magni, Kamil Grzyb, Paul MA. Antony, Rejko Krüger, Alexander Skupin, Silvia Bolognin, View ORCID ProfileJens C. Schwamborn
doi: https://doi.org/10.1101/589598
Lisa M. Smits
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Stefano Magni
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Kamil Grzyb
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Paul MA. Antony
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Rejko Krüger
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Alexander Skupin
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
2University California San Diego, La Jolla, CA, USA
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Silvia Bolognin
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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Jens C. Schwamborn
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux Luxemboug
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  • ORCID record for Jens C. Schwamborn
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Abstract

Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organisation and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA-sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, and glutamatergic neurons. Recapitulating these in vivo features makes hMOs an excellent tool for in vitro disease phenotyping and drug discovery.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 28, 2019.
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Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Lisa M. Smits, Stefano Magni, Kamil Grzyb, Paul MA. Antony, Rejko Krüger, Alexander Skupin, Silvia Bolognin, Jens C. Schwamborn
bioRxiv 589598; doi: https://doi.org/10.1101/589598
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Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Lisa M. Smits, Stefano Magni, Kamil Grzyb, Paul MA. Antony, Rejko Krüger, Alexander Skupin, Silvia Bolognin, Jens C. Schwamborn
bioRxiv 589598; doi: https://doi.org/10.1101/589598

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