Neurons and astrocytes have distinct organelle signatures and responses to stress

Rhoads, S. N.; Dong, W.; Hsu, C.-H.; Mfulama, N. R.; Ragusa, J. V.; Ye, M.; Henrie, A.; Zanellati, M. C.; Diering, G. H.; Cohen, T. J.; Cohen, S.

doi:10.1101/2024.10.30.621066

bioRxiv · 10.1101/2024.10.30.621066

Neurons and astrocytes have distinct organelle signatures and responses to stress

Rhoads, S. N.·Dong, W.·Hsu, C.-H.·Mfulama, N. R.·Ragusa, J. V.·Ye, M.·Henrie, A.·Zanellati, M. C.·Diering, G. H.·Cohen, T. J.·Cohen, S.

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Abstract

Neurons and astrocytes play critical yet divergent roles in brain physiology and neurological conditions. Intracellular organelles are integral to cellular function. However, an in-depth characterization of organelles in live brain cells has not been performed. Here, we used multispectral imaging to simultaneously visualize six organelles - endoplasmic reticulum (ER), lysosomes, mitochondria, peroxisomes, Golgi, and lipid droplets - in live primary rodent neurons and astrocytes. We generated a dataset of 173 Z-stack and 99 time-lapse images accompanied by quantitative analysis of 1418 metrics (the "organelle signature"). Comparative analysis revealed clear cell-type specificity in organelle morphology and interactions. Neurons were characterized by prominent mitochondrial composition and interactions, while astrocytes contained more lysosomes and lipid droplet interactions. Additionally, neurons displayed a more robust organelle response than astrocytes to acute oxidative or ER stress. Our data provide a systems-level characterization of neuron and astrocyte organelles that can be a reference for understanding cell- type-specific physiology and disease.

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Rhoads, S. N., Dong, W., Hsu, C.-H., Mfulama, N. R., Ragusa, J. V., Ye, M., Henrie, A., Zanellati, M. C., Diering, G. H., Cohen, T. J., Cohen, S.. 2024-10-30. Neurons and astrocytes have distinct organelle signatures and responses to stress. https://doi.org/10.1101/2024.10.30.621066

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