RT Journal Article
SR Electronic
T1 Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.29.178202
DO 10.1101/2020.06.29.178202
A1 Alexandr A. Kalinin
A1 Xinhai Hou
A1 Alex S. Ade
A1 Gordon-Victor Fon
A1 Walter Meixner
A1 Gerald A. Higgins
A1 Jonathan Z. Sexton
A1 Xiang Wan
A1 Ivo D. Dinov
A1 Brian D. Athey
YR 2020
UL http://biorxiv.org/content/early/2020/06/29/2020.06.29.178202.abstract
AB 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 structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.Competing Interest StatementThe authors have declared no competing interest.