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

Lisa M. Smits, Stefano Magni, Kaoru Kinugawa, Kamil Grzyb, Joachim Luginbühl, Sonia Sabate-Soler, Silvia Bolognin, Jay W. Shin, Eiichiro Mori, Alexander Skupin, Jens C. Schwamborn*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)463-476
Number of pages14
JournalCell and Tissue Research
Volume382
Issue number3
DOIs
Publication statusPublished - Dec 2020
Externally publishedYes

Keywords

  • Electrophysiological activity
  • Midbrain organoids
  • Neural stem cells
  • Neuronal subtypes
  • Single-cell RNA sequencing

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