上海科技大学知识管理系统

Nuclear deformation is an essential phenomenon allowing cell migration and can be observed in association with pathological conditions such as laminopathies, neurodegenerative disorders and diabetes. Abnormal nuclear morphologies are a hallmark of cancer progression and nuclear deformability is a necessary feature for metastatic progression. Nevertheless, the cellular processes and the key molecular components controlling nuclear shape are poorly understood, in part due to a limited availability of assays that allow high-throughput screening of nuclear morphology-phenotypes. In this study, we explore the application of micropillared substrates as the basis for a phenotypic screening platform aimed at identifying novel determinants of nuclear morphology. We designed PDMS substrates to maximize simplicity in image acquisition and analyses, and in a small-scale screening of inhibitors targeting chromatin-modifying enzymes, we identify histone deacetylation as cellular process involved in nuclear deformation. With increasingly specific targeting approaches, we identify HDAC2 as a novel player in controlling nuclear morphology through gene transcription repression. This study shows the effectiveness of micropillar-based substrates to act as phenotypic drug screening platforms and opens a new avenue in the identification of genes involved in determining the nuclear shape.