Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells

The formin mDia2 is localized to the nucleus of the mesenchymal stem cell, while mDia1 is restricted to the cytoplasm. mDia2 is critical to function of the actin ‐lamin nucleoskeleton where it inhibits lineage commitment. When mDia2 is deficient, the lamin B1 nucleoskeleton is disrupted, activating osteogenesis, but not adipogenesis. AbstractNuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow derived MSCs, the principal diaphanous ‐related formin Diaph3 (mDia2) is present in the nucleus and regulates intranuclear actin polymerization, while Diaph1 (mDia1) is localized to the cytoplasm and controls cytoplasmic actin polymerization. We here show that mDia2 can be used as a tool to query actin‐lamin nucleoskeletal structure. Silencing mDia2 affected the nucleoskeletal lamin scaffold, altering nuclear morphology without affecting cytoplasmic actin cytoskeleton, and promoted MSC differentiation. Attempting to target intranuclear actin polymerization by silencing mDia2 led to a profound loss in lamin B1 nuclear envelope s tructure and integrity, increased nuclear height, and reduced nuclear stiffness without compensatory changes in other actin nucleation factors. Loss of mDia2 with the associated loss in lamin B1 promoted Runx2 transcription and robust osteogenic differentiation and suppressed adipogenic differentiat ion. Hence, mDia2 is a potent tool to query intranuclear actin‐lamin nucleoskeletal structure, and its pres...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics Source Type: research