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

• Published in: Cell and tissue research Vol. 382; no. 3; pp. 463 - 476
• Main Authors: Smits, Lisa M., Magni, Stefano, Kinugawa, Kaoru, Grzyb, Kamil, Luginbühl, Joachim, Sabate-Soler, Sonia, Bolognin, Silvia, Shin, Jay W., Mori, Eiichiro, Skupin, Alexander, Schwamborn, Jens C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2020; Springer; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Dopamine; Dopamine receptors; Electrophysiology; Ethylenediaminetetraacetic acid; GABA; Glutamatergic transmission; Health maintenance organizations; Human Genetics; Mesencephalon; Molecular Medicine; Neurons; Organoids; Phenotyping; Proteomics; Regular; Regular Article; Ribonucleic acid; RNA; RNA sequencing; Serotonin; Stem cells; γ-Aminobutyric acid; Neural stem cells; Midbrain organoids; Single-cell RNA sequencing; Neuronal subtypes; Electrophysiological activity
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-020-03249-y

Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organization 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, glutamatergic and serotonergic neurons. Recapitulating these in vivo features makes hMOs an excellent tool for in vitro disease phenotyping and drug discovery.