Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

• Published in: Stem cell reports Vol. 8; no. 5; pp. 1144 - 1154
• Main Authors: Monzel, Anna S., Smits, Lisa M., Hemmer, Kathrin, Hachi, Siham, Moreno, Edinson Lucumi, van Wuellen, Thea, Jarazo, Javier, Walter, Jonas, Brüggemann, Inga, Boussaad, Ibrahim, Berger, Emanuel, Fleming, Ronan M.T., Bolognin, Silvia, Schwamborn, Jens C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.05.2017; Elsevier
• Subjects: Cells, Cultured; Dopaminergic Neurons - cytology; Humans; Mesencephalon - cytology; midbrain; Myelin Sheath - metabolism; neural stem cells; Neural Stem Cells - cytology; Neuroepithelial Cells - cytology; Neurogenesis; organoid; Organoids - cytology; Organoids - metabolism; Parkinson’s disease; stem cells; stem cells; midbrain; neural stem cells; Parkinson’s disease; organoid
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.03.010

Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson’s disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy development. [Display omitted] •Generation of a human in vitro midbrain model from neural precursor cells•Midbrain organoids show neuronal, astroglial, and oligodendrocyte differentiation•Midbrain organoids contain spatially organized groups of dopaminergic neurons•Detection of synaptic connections, electrophysiological activity, and myelination Monzel and colleagues demonstrate the derivation of human midbrain-specific brain organoids from lineage-restricted human neural precursor cells. They further show that the stem cells can self-organize into spatially patterned groups of dopaminergic neurons. Moreover, the presence of synaptic connections, myelinated of neurites, and electrophysiological activity of neurons is demonstrated.