Open AccessKnockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells
Author(s) -
Sankaran Jeyantt S.,
Sen Buer,
Dudakovic Amel,
Paradise Christopher R.,
Perdue Tony,
Xie Zhihui,
McGrath Cody,
Styner Maya,
Newberg Joshua,
Uzer Gunes,
Wijnen Andre J.,
Rubin Janet
Publication year - 2020
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3098
Subject(s) - biology , lamin , microbiology and biotechnology , formins , nuclear lamina , stem cell , mdia1 , actin , actin cytoskeleton , transcription factor , cell , nuclear protein , cytoskeleton , genetics , nucleus , gene
Nuclear 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, whereas 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 structure 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 differentiation. Hence, mDia2 is a potent tool to query intranuclear actin‐lamin nucleoskeletal structure, and its presence serves to retain multipotent stromal cells in an undifferentiated state.