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

Related Web Links

N/A

Keywords

Parvalbumin-positive, interneurons, organoid, brain, neuron, cortical

Technology Reference

CZB-193F-PC, SF2021-112

Patent Information:
For Information, Contact:
CZBiohub Admin
CZ Biohub
ip@czbiohub.org
Inventors:
Mohammed Mostajo-Radji
Alex Pollen
Keywords:
Brain
Cortical
Interneurons
Neuron
Organoid
Parvalbumin-Positive