3D human co-culture to model neuron-astrocyte interactions in tauopathies
Vrije Universiteit Amsterdam, Amsterdam, Netherlands
Intraneuronal tau aggregation is the major pathological feature of neurodegenerative tauopathies. To model the interaction between neurons and astrocytes in tauopathies, a 3D human neuron/astrocyte co-culture model was established here, containing homogeneous populations of hiPSC-derived neurons and primary human astrocytes in microtiter plate format. Using confocal, electron, and live microscopy, neurons in 3D coculture were shown to form pre- and postsynapses and exhibit spontaneous calcium transients within 4 weeks. Astrocytes in 3D co-culture exhibited a bipolar and stellate morphology with extensive processes enveloping neuronal somas, spatially aligned with axons and dendrites, and found perisynaptically. The complex morphology of astrocytes and interaction with neurons in 3D coculture mirrored that of the human brain, indicating the potential of the model to study physiological and pathological neuron-astrocyte interactions in vitro. In addition, the authors developed a method to introduce seed-independent intraneuronal tau aggregation in 3D co-culture, allowing the study of neuron-astrocyte interactions in early tau pathogenesis. Overall, these data provide evidence for the utility of this rapid, miniaturized, and standardized 3D model for cell type-specific manipulations, such as intraneuronal pathology associated with neurodegenerative diseases.
A 3D human co-culture to model neuron-astrocyte interactions in tauopathies
Added on: 04-27-2023