METHODS FOR GENERATING PARVALBUMIN-POSITIVE INTERNEURONS

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