Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells
| Autor: | Mayuri Vijay Thete, Jin-Young Park, Alyssa Puno, Matthew H. Porteus, Yuki Miura, Samuel H. Lee, Fikri Birey, Min-Yin Li, Omer Revah, Kazuya Ikeda, Sergiu P. Pașca |
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| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
Cellular differentiation Biomedical Engineering Bioengineering Stimulation Striatum Biology Optogenetics Medium spiny neuron Applied Microbiology and Biotechnology Models Biological 03 medical and health sciences 0302 clinical medicine Pregnancy Organoid Humans Induced pluripotent stem cell 030304 developmental biology Cerebral Cortex 0303 health sciences Corpus Striatum Organoids Phenotype nervous system Forebrain Molecular Medicine Calcium Female Nerve Net Neuroscience 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Nature biotechnology. 38(12) |
| ISSN: | 1546-1696 |
| Popis: | Cortico-striatal projections are critical components of forebrain circuitry that regulate motivated behaviors. To enable the study of the human cortico-striatal pathway and how its dysfunction leads to neuropsychiatric disease, we developed a method to convert human pluripotent stem cells into region-specific brain organoids that resemble the developing human striatum and include electrically active medium spiny neurons. We then assembled these organoids with cerebral cortical organoids in three-dimensional cultures to form cortico-striatal assembloids. Using viral tracing and functional assays in intact or sliced assembloids, we show that cortical neurons send axonal projections into striatal organoids and form synaptic connections. Medium spiny neurons mature electrophysiologically following assembly and display calcium activity after optogenetic stimulation of cortical neurons. Moreover, we derive cortico-striatal assembloids from patients with a neurodevelopmental disorder caused by a deletion on chromosome 22q13.3 and capture disease-associated defects in calcium activity, showing that this approach will allow investigation of the development and functional assembly of cortico-striatal connectivity using patient-derived cells. Organoids representing the human striatum are generated and used to build circuits in cortico-striatal assembloids. |
| Databáze: | OpenAIRE |
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