Medial Ganglionic Eminence Organoid Modeling Service

The Medial Ganglionic Eminence (MGE) is a critical transient structure in the developing brain, responsible for generating a large population of inhibitory interneurons. These interneurons are essential for establishing and maintaining proper neural circuit function. Creative Biolabs provides a suite of specialized services centered on human MGEOs (Medial Ganglionic Eminence Organoids), designed to empower researchers in their investigations of brain development, neurological disease modeling, and drug discovery.

Our Core Service Areas

1. MGEOs Generation: We offer robust and reproducible generation of human MGEOs (Medial Ganglionic Eminence Organoids) from pluripotent stem cells (PSCs). Our protocols ensure the formation of MGEOs that closely mimic the in vivo development of the MGE. We can work with customer-provided cell lines or supply thoroughly characterized lines.

Fig.1 Bright-field imaging reveals the morphological changes of ihtc-03-derived hMGEOs at distinct developmental points.¹

2. MGEOs Characterization: We provide comprehensive characterization services to validate the identity, purity, and developmental stage of MGEOs. Our analytical capabilities include:

• Immunohistochemistry: Spatial and cell-type specific protein expression analysis.

Fig.2 Immunostaining of day-40 hMGEOs for MGE marker NKX2-1 (red) and nuclei (Hoechst, blue).¹

• Electrophysiology: Functional analysis of MGE neurons, including action potential firing and synaptic activity.

3. MGEOs-Based Assays: We offer specialized assays utilizing MGEOs to address specific research questions:

• Interneuron Migration Assays: Modeling the migration of MGE-derived interneurons into other brain regions using co-culture or fusion with region-specific organoids.
• Disease Modeling: Generation of MGEOs from patient-derived induced pluripotent stem cells (iPSCs) to model neurological disorders linked to MGE dysfunction.
• Drug Screening: Utilizing MGEOs as a platform for compound screening and toxicity testing.

4. Advanced Organoid Services:

• Vascularized MGEOs: Implementation of 3D-printed artificial vessels to enhance MGEOs survival, growth, and maturation by improving oxygen and nutrient delivery.
• Multi-regional Assembloids: Generation of complex assembloids incorporating MGEOs with other brain region organoids (e.g., cortex, striatum) to study inter-regional interactions and circuit formation.
• Genetic Manipulation: Introduction of specific genetic modifications (e.g., CRISPR-Cas9 mediated gene editing) to study gene function in MGE development and disease.

Example Service Detail: Modeling Neurodevelopmental Disorders with Patient-Derived MGEOs

Many neurodevelopmental disorders, including schizophrenia and epilepsy, are associated with disruptions in the development or function of GABAergic interneurons, the primary cell type generated in the MGE.

Our company offers a service to generate MGEOs from patient-derived iPSCs to model these disorders in vitro. This approach allows for the recapitulation of patient-specific cellular phenotypes and the study of disease mechanisms.

The process involves:

1. iPSC Generation: Generation of iPSCs from patient tissue samples (e.g., skin fibroblasts).
2. MGEO Differentiation: Differentiation of patient-derived iPSCs into MGEOs using our optimized protocols.
3. Characterization of Disease Phenotypes: Comprehensive analysis of patient-derived MGEOs to identify cellular and molecular phenotypes associated with the disorder. This can include:
   • Analysis of interneuron subtype distribution.
   • Assessment of synaptic function and network activity.
   • Examination of gene expression profiles and protein levels.
4. Comparative Analysis: Comparison of patient-derived MGEOs with control MGEOs generated from healthy individuals to pinpoint disease-specific alterations.

This service provides a powerful platform for:

• Disease Mechanism Studies: Investigating the cellular and molecular basis of neurodevelopmental disorders.
• Drug Discovery: Screening potential therapeutic compounds that can rescue disease phenotypes in patient-derived MGEOs.

By utilizing our expertise in MGEOs technology and iPSC-derived disease modeling, researchers can gain crucial insights into the pathogenesis of neurological disorders and accelerate the development of effective treatments.

Our Workflow

Accelerate Your Research with Human-Relevant Models

Whether exploring fundamental neurodevelopment, disease mechanisms, or therapeutic strategies, our MGEOs platform provides unparalleled resolution of human-specific interneuron biology. Contact us to design a project tailored to your research goals.

Reference

1. Wang, Yuanyuan et al. “Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development.” Journal of biomedical research vol. 36,4 (2022): 242-254. doi:10.7555/JBR.36.20220074. Distributed under Open Access License CC BY 4.0. The original image was modified.