Cerebellum Organoid Modeling Service

Our Cerebellum Organoid Modeling Service provides advanced 3D human cerebellar organoids (hCerOs) derived from patient-specific iPSCs or engineered cell lines. Utilizing CRISPR-Cas9 and optimized protocols, Creative Biolabs generates organoids with functional Purkinje cells, granular neurons, and human-specific developmental features. These models enable precise study of cerebellar disorders, drug testing, and mechanistic research, bridging the gap between in vitro and in vivo neuroscience. Our platform accelerates breakthroughs in understanding and treating ataxias, autism, and brain cancers.

Introduction

The cerebellum, a vital brain region, plays crucial roles in motor coordination, cognitive functions, and emotional processing. Dysfunction in cerebellar development or activity is strongly linked to neurological disorders such as spinocerebellar ataxia (SCA), autism spectrum disorders, and medulloblastoma. Traditional research models, including animal studies, often fall short in replicating human-specific cerebellar characteristics, such as neuronal subtype ratios and the complexity of its folded structure (foliation). This limitation hinders their translational relevance.

Recent breakthroughs in cerebellar organoid technology have revolutionized the study of human cerebellar biology and disease. By utilizing human induced pluripotent stem cells (iPSCs), researchers have developed three-dimensional human cerebellar organoids (hCerOs) that closely mimic fetal cerebellar development, including the generation of functional Purkinje cells – the primary output neurons of the cerebellar cortex. These hCerOs replicate the cellular diversity, layered organization, and functional neural networks observed in vivo, offering unprecedented opportunities to model diseases, screen therapeutics, and investigate human-specific neurodevelopmental mechanisms.

At Creative Biolabs, we integrate cutting-edge protocols to provide researchers with robust, physiologically relevant tools for advancing cerebellar research.

Key Advantages

• Mirroring Human Cerebellar Complexity: Diverse Cell Populations

Our hCerOs faithfully replicate the intricate cellular composition of the developing human cerebellum, generating all major cell types, including granule cell precursors, Purkinje neurons, and human-specific rhombic lip-derived progenitors. This cellular diversity closely reflects in vivo developmental stages, enabling in-depth studies of cell-type-specific mechanisms and interspecies differences. Unlike traditional models, our organoids capture unique human cerebellar features, such as distinct neuronal subtype ratios and structural complexity, making them ideal for investigating neurodevelopmental disorders and evolutionary distinctions.

• Recreating Native Architecture: Structured Organization

Our hCerOs self-organize into spatially distinct ventricular and rhombic lip progenitor zones, closely resembling the layered organization of the fetal cerebellum. Through optimized culture conditions, we achieve patterning reminiscent of the external granular layer (EGL) and Purkinje cell layer (PCL), which are critical for studying neuronal migration and circuit formation. This structural fidelity ensures that crucial cellular interactions and microenvironmental cues are preserved, providing a physiologically relevant system for disease modeling and drug screening.

• Capturing Functional Activity: Maturation and Network Integration

Long-term cultured hCerOs develop synchronized neuronal networks exhibiting spontaneous calcium oscillations and action potential firing, indicating functional synaptic connectivity. Our platform supports advanced electrophysiological studies and optogenetic manipulation, allowing real-time interrogation of cerebellar circuitry. These functional networks provide a dynamic model to explore neurotoxicity, circuit dysfunction in cerebellar ataxias, and the impact of genetic mutations on neuronal activity.

Our Comprehensive Cerebellum Organoid Services

We offer end-to-end solutions for generating, characterizing, and applying cerebellar organoids in both research and drug development:

1. Customized hCerO Generation

• Differentiation of iPSCs/ESCs into cerebellar organoids using optimized protocols.
• Incorporation of human-specific morphogens (e.g., FGF8b, SDF1α) to enhance rhombic lip and ventricular zone patterning.

2. Precise Disease Modeling

• Development of patient-derived organoids for hereditary ataxias, medulloblastoma, and neurodevelopmental disorders.
• CRISPR-Cas9-mediated gene editing to introduce or correct disease-associated mutations (e.g., ATXN3 CAG repeat expansion).

3. Advanced Drug Screening & Toxicity Testing

• High-throughput platforms to evaluate neuroprotective compounds, small molecules, or gene therapies.
• Functional readouts including calcium imaging, electrophysiology, and apoptosis assays.

4. In-Depth Characterization

• Immunohistochemistry for key markers like ATOH1 (granule cells), CALB1 (Purkinje cells), and BARHL1 (progenitors).
• Electrophysiological analysis of Purkinje cell activity and network synchronization.

5. Long-Term Maturation & Co-Culture Systems

• Extended culturing (up to 8 months) to achieve advanced neuronal maturation.
• Integration with organoids from other brain regions (e.g., cortical or midbrain) to study cerebellar connectivity.

Our Workflow

Partner with Us to Advance Your Cerebellar Research

Leverage our expertise in cutting-edge cerebellar organoid technology to accelerate your research into brain development, disease mechanisms, and therapeutic discovery. Contact us today to design a tailored solution for your project.

Reference

1. Ryu, Seungmi et al. “Modeling Friedreich's ataxia with Bergmann glia-enriched human cerebellar organoids.” bioRxiv : the preprint server for biology 2025.05.16.654315. 16 May. 2025, doi:10.1101/2025.05.16.654315. Preprint. Distributed under Open Access License CC0. The original image was modified.