iPSC-derived Glutamatergic Neuron Generation Service

Glutamatergic neurons are a major class of neurons that release the neurotransmitter glutamate. Glutamate is the primary excitatory neurotransmitter in the central nervous system, playing a key role in neuronal signaling pathways involved in cognition, memory, and learning.

These neurons can be derived from human induced pluripotent stem cells (iPSCs) through directed differentiation protocols. iPSCs are generated by reprogramming somatic cells, like skin or blood cells, back into a pluripotent stem cell state. From this pluripotent state, the cells can then be coaxed into becoming glutamatergic neurons. Creative Biolabs offers custom iPSC differentiation services to generate glutamatergic and other neuronal subtypes according to your research needs.

iPSC-derived Glutamatergic Neurons Offer Several Advantages Over Other Models

• Renewable source avoiding ethical concerns with fetal-derived cells

iPSCs can be generated from adult somatic cells, providing a renewable source of cells without the need for fetal tissue.

• Obtain homogeneous populations of glutamatergic neuron subtypes

Differentiation from iPSC lines can produce pure cultures of defined glutamatergic neurons.

• Ability to generate patient-specific cell lines to model diseases

By reprogramming cells from patients with a genetic disease, researchers can create iPSC-derived neurons that carry the patient's specific genetic mutations. This allows the modeling of the disease phenotypes in a dish.

• Scalable production for high-throughput screening applications

The unlimited self-renewal of iPSCs enables large-scale production of glutamatergic neurons for applications like drug screening in multi-well plates.

• Physiologically relevant human neurons for disease modeling

Unlike animal models or immortalized cell lines, iPSC-derived neurons are human cells that can better recapitulate human disease physiology

These iPSC-derived Glutamatergic Neurons Are Commonly Used For

• Modeling glutamate-related neurological diseases like Alzheimer's, Huntington's, and ALS.
• Studying mechanisms of neurotransmission, synapse formation, and neuronal networks.
• Screening potential therapeutic compounds that modulate glutamatergic signaling.
• Toxicology studies evaluating the effects of drugs/compounds on human neurons.

Common Assays With iPSC-derived Glutamatergic Neurons

• Immunocytochemistry to visualize proteins of interest

Antibody labeling allows visualization of neuron-specific markers or disease-related proteins.

• Gene expression analysis (RNA-seq, qPCR)

Transcriptomic studies examine gene expression changes associated with diseases or drug treatments.

• Neurite outgrowth and neurodevelopmental assays

Assays that examine the ability of neurons to properly extend neurites and mature during development.

• Neurotransmitter release and uptake assays

Techniques to quantify release of glutamate or uptake by glutamate transporters on the neurons.

• Electrophysiology to study electrical firing properties

Patch-clamp and multi-electrode array (MEA) recordings measure the electrical activity of the neurons.

• Calcium imaging to measure neuronal activity

Fluorescent calcium indicators allow visualization of calcium influx into neurons upon stimulation, indicating neuronal firing.

Glutamatergic Neurons Have Been Implicated In Many Neurological And Neurodegenerative Diseases

• Alzheimer's Disease: Excitotoxicity via overstimulation of glutamate receptors.

The buildup of amyloid-beta protein aggregates may disrupt glutamate signaling, causing excitotoxic neuronal death.

• Huntington's Disease: Mutant huntingtin affects glutamate signaling.

Mutant huntingtin protein impairs glutamate transporter function and NMDA receptor activity.

• Amyotrophic Lateral Sclerosis (ALS): Glutamate transporter defects.

Mutations in glutamate transporters lead to excitotoxic motor neuron degeneration in ALS patients.

• Epilepsy: Imbalance of excitatory/inhibitory neurotransmission.

Excessive glutamatergic signaling can disturb the balance with inhibitory GABA neurons, causing seizures.

• Stroke: Excitotoxic neuronal death after ischemic injury.

During the stroke, impaired glutamate clearance results in over-activation of glutamate receptors and neuron death.

iPSC-derived glutamatergic neurons serve as a powerful tool for neuroscience research, disease modeling, drug discovery, and toxicology studies related to neurological disorders involving glutamatergic dysfunction. iPSC models allow the study of patient-specific glutamatergic neurons harboring genetic mutations relevant to these diseases. External compounds, gene editing, or other treatments can be applied to elucidate pathological mechanisms and test potential therapeutics.

Creative Biolabs has extensive experience generating iPSC-derived neuronal cultures tailored to our customers' requirements. Let us guide you through your experimental investigations and help advance your understanding of neural development and connectivity.

Reference

1. Tukker, Anke M et al. "Human iPSC-derived neuronal models for in vitro neurotoxicity assessment." Neurotoxicology. 2018;67:215-225. Distributed under Open Access license CC BY 4.0 without modification.