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Differentiation of ciliated human midbrain-derived LUHMES neurons
Gilbert Lauter1, Andrea Coschiera1, Masahito Yoshihara1
1Karolinska Institute, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden.
Journal of Cell Science
|October 29, 2020
Summary
A new human neuronal cell model, LUHMES, allows easy study of cilia development and function from progenitor to mature neuron stages. This model aids research into ciliopathies and brain development.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Cilia are crucial in many cell types, including neurons, but neuronal cilia biology is poorly understood.
- Ciliopathies, linked to defective cilia, cause various diseases with brain phenotypes, yet underlying pathways remain unclear.
- A readily maintainable, ciliated human neuronal cell model is lacking for studying these processes.
Purpose of the Study:
- To introduce and characterize the Lund human mesencephalic (LUHMES) cell line as a model for neuronal cilia research.
- To investigate ciliogenesis and neuronal differentiation pathways using LUHMES cells.
- To provide a tool for studying the molecular basis of ciliopathies affecting the brain.
Main Methods:
- Utilized the LUHMES cell line, derived from human fetal mesencephalon.
- Cultured and differentiated LUHMES cells to study distinct developmental stages (progenitor, differentiating neuron).
- Employed RNA-sequencing timecourse analyses to identify gene-regulatory networks involved in ciliogenesis and axon outgrowth.
Main Results:
- LUHMES cells possess a single primary cilium throughout progenitor and neuronal differentiation stages.
- Developmental stages are separable within one day by changing culture conditions.
- Sonic hedgehog (SHH) signaling pathway is active during LUHMES neuronal differentiation.
- RNA-sequencing revealed key molecular pathways and gene networks for ciliogenesis and axon outgrowth.
- LUHMES cell gene expression dynamics accurately reflect human fetal midbrain in vivo development.
Conclusions:
- The LUHMES cell line provides an accessible and effective model for studying human neuronal cilia biology across multiple developmental stages.
- This model facilitates research into the molecular mechanisms underlying ciliogenesis, neuronal differentiation, and axon development.
- LUHMES cells offer a valuable platform for investigating the biological pathways implicated in brain-related ciliopathies.
