@article{c8c677b9408e4f9c9c5a846bfe629db2,
title = "Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells",
abstract = "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.",
keywords = "intranuclear actin, mDia2, nucleoskeleton, stem cell fate",
author = "Sankaran, {Jeyantt S.} and Buer Sen and Amel Dudakovic and Paradise, {Christopher R.} and Tony Perdue and Zhihui Xie and Cody McGrath and Maya Styner and Joshua Newberg and Gunes Uzer and {van Wijnen}, {Andre J.} and Janet Rubin",
note = "Funding Information: We would like to thank the Microscope Services Laboratory, Department of Pathology and Laboratory Medicine, UNC Chapel Hill, which is supported in part by P30 CA016086 Cancer Center Core Support Grant to UNC Lineberger Comprehensive Cancer Center. This study was supported by Grants AR066616 (to J.R.), P20GM109095 (to G.U.), and R01 AR049069 (to A.v.W.). Funding Information: We would like to thank the Microscope Services Laboratory, Department of Pathology and Laboratory Medicine, UNC Chapel Hill, which is supported in part by P30 CA016086 Cancer Center Core Support Grant to UNC Lineberger Comprehensive Cancer Center. This study was supported by Grants AR066616 (to J.R.), P20GM109095 (to G.U.), and R01 AR049069 (to A.v.W.). Funding Information: J.S.S.: conceived, designed and ran experiments, collected, analyzed and interpreted data, wrote and approved the manuscript; B.S., A.D., C.R.P., J.N., and Z.X.: ran experiments, collected, analyzed and interpreted data, and edited manuscript; T.P.: super resolution microscopy imaging and interpretation and edited manuscript; C.M. and M.S.: edited manuscript; G.U. and A.V.W.: designed experiments, interpreted data, and edited manuscript; J.R.: financial support, conceived, and designed experiments, interpreted data, wrote, and approved the manuscript. Publisher Copyright: {\textcopyright}AlphaMed Press 2019",
year = "2020",
month = jan,
day = "1",
doi = "10.1002/stem.3098",
language = "English (US)",
volume = "38",
pages = "102--117",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "Wiley-Blackwell",
number = "1",
}