METHODS FOR GENERATING PARVALBUMIN-POSITIVE INTERNEURONS
Researchers at UCSF and have developed a method for generating an enriched population of parvalbumin-positive interneurons.
Parvalbumin-positive interneurons are the largest subpopulation of inhibitory interneurons in the cerebral cortex, and are involved in a variety of neurodevelopmental and neurodegenerative disorders. Based on their important functions in the brain, there is a need in the field for a method to generate parvalbumin-positive interneurons for further study.
Stage of Research
The inventors have developed a method for generating an enriched population of parvalbumin-positive interneurons. This comprises culturing a population of mouse primary neuronal progenitors in a human brain organoid or a primary brain slice of human origin, wherein the mouse primary neuronal progenitors differentiate into parvalbumin-positive interneurons in the brain organoid or the primary brain slice, thereby generating an enriched population of parvalbumin-positive interneurons.
Applications
- Identifying host environment biases for medial ganglionic eminence (MGE)-interneuron fate
- Development of chimeric cortical organoid models for longitudinal interrogation of circuit assembly
- Determining if human organoids can recapitulate parvalbumin-positive (PV) fate bias
- Non-cell-autonomous instruction of PV fate
- Reprogramming of post-mitotic SST-positive interneurons to a PV fate
Advantages
- Longer-term neuron viability than human organotypic cortical cultures
- Use of mouse interneurons integrated into 3D cortical human organoids is necessary and sufficient to instruct PV fate in MGE progenitors, while other co-culture methods (i.e. dissociated cortical cells) fail to do so
Stage of Development
Research – in vitro
Publications
WO2022/266097
Related Web Links
N/A
Keywords
Parvalbumin-positive, interneurons, organoid, brain, neuron, cortical
Technology Reference
CZB-193F-PC, SF2021-112