Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells

BioRxiv : the Preprint Server for Biology
Alexandr A KalininBrian D Athey


Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical implications as human therapeutics and cellular reprogramming agents. They induce chromatin re-organization associated with changes in cell nuclear morphology. Current approaches aiming to quantify these changes so far have been limited to basic 2D measures. Here, we quantified changes in 3D nuclear morphology of primary human astrocyte cells treated with VPA for 7 days (hence, 4D). We compared volumetric and surface-based 3D shape representations of cell nuclei and selected subset of features that jointly discriminated between normal and treated cells with 85% accuracy on day 7. Over time, VPA-treated nuclear morphologies progressed towards larger size and higher shape irregularity. On day 7, all 11 selected size and shape descriptors demonstrated significant difference between treated and untreated nuclear morphologies, including 22.5% increase in volume and 8.3% reduction in extent (shape regularity) for VPA-treated nuclei. Overall, we showed that 4D surface morphometry accurately characterizes the temporal changes in astrocyte nuclear form that are reflective of the underlying valproate-induced chromatin re-organization. These nuclear struc...Continue Reading

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