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

Sankaran, Jeyantt Srinivas; Sen, Buer; Dudakovic, Amel; Paradise, Christopher R.; Perdue, Tony D.; McGrath, Cody; Styner, Martin; Newberg, Joshua; Uzer, Gunes; Wijnen, André J. van; Rubin, Janet

doi:10.1002/stem.3098

Cited by 17 publications

(10 citation statements)

References 54 publications

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“…We showed that during the cell division of CFU-Es, the localization of mDia2 changed from the nucleus to the cytoplasmic membrane. This result is in agreement with previous findings obtained using human and mouse cells 29 , 30 . Moreover, we found that the localization of mDia2 remained unchanged in the nucleus during the enucleation of erythroblasts.…”

Section: Discussionsupporting

confidence: 94%

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Ubukawa

Goto

Asanuma

et al. 2020

Sci Rep

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The molecular mechanisms involved in the terminal differentiation of erythroblasts have been elucidated by comparing enucleation and cell division. Although various similarities and differences between erythroblast enucleation and cytokinesis have been reported, the mechanisms that control enucleation remain unclear. We previously reported that dynein and microtubule-organizing centers mediated the polarization of nuclei in human erythroblasts. Moreover, the accumulation of F-actin was noted during the enucleation of erythroblasts. Therefore, during enucleation, upstream effectors in the signal transduction pathway regulating dynein or actin, such as cell division control protein 42 homolog (Cdc42), may be crucial. We herein investigated the effects of the Cdc42 inhibitor, CASIN, on cytokinesis and enucleation in colony-forming units-erythroid (CFU-Es) and mature erythroblasts (day 10). CASIN blocked the proliferation of CFU-Es and their enucleation in a dose-dependent manner. Dynein adopted an island-like distribution in the cytoplasm of non-treated CFU-Es, but was concentrated near the nucleus as a dot and co-localized with γ-tubulin in CASIN-treated cells. CASIN blocked the accumulation of F-actin in CFU-Es and day 10 cells. These results demonstrated that Cdc42 plays an important role in cytokinesis, nuclear polarization and nuclear extrusion through a relationship with dynein and actin filament organization during the terminal differentiation of erythroblasts.

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Section: Discussionsupporting

confidence: 94%

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Ubukawa

Goto

Asanuma

et al. 2020

Sci Rep

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“…In contrast, knocking down mDia2 leads to a decrease in osteogenesis, while silencing of mDia2 has no effect on osteogenesis [57]. Knocking down mDia2 also leads to a decrease in the expression and structure of lamin-B1 [58]. However, it is not clear whether mDia2 knockdown decreases osteogenesis directly through nuclear actin or indirectly through lamin-B1.…”

Section: Actin Cytoskeleton and Rho Pathwaymentioning

confidence: 98%

“…In addition to being found at the periphery, lamin A/C and lamin-B1 interact with chromatin in the nucleoplasm [60,61]. This suggests that mDia2-mediated actin polymerization affects lamin integrity and composition, which might be crucial for MSC differentiation [58].…”

Section: Actin Cytoskeleton and Rho Pathwaymentioning

confidence: 99%

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

et al. 2020

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Mesenchymal stem cells (MSCs) have the capacity to differentiate into multiple lineages including osteogenic and adipogenic lineages. An increasing number of studies have indicated that lineage commitment by MSCs is influenced by actin remodeling. Moreover, actin has roles in determining cell shape, nuclear shape, cell spreading, and cell stiffness, which eventually affect cell differentiation. Osteogenic differentiation is promoted in MSCs that exhibit a large spreading area, increased matrix stiffness, higher levels of actin polymerization, and higher density of stress fibers, whereas adipogenic differentiation is prevalent in MSCs with disrupted actin networks. In addition, the mechanical properties of F-actin empower cells to sense and transduce mechanical stimuli, which are also reported to influence differentiation. Various biomaterials, mechanical, and chemical interventions along with pathogeninduced actin alteration in the form of polymerization and depolymerization in MSC differentiation were studied recently. This review will cover the role of actin and its modifications through the use of different methods in inducing osteogenic and adipogenic differentiation.

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“…48h after siRNA treatment, cell nuclei were isolated, plated onto 0.1% Poly-L-Lysine coated plates for adherence and subjected to AFM testing to obtain force-displacement curves as we reported previously ( Fig. 1a ) 19 . As shown in immunolabeled nuclei images ( Fig.…”

Section: Data Collection Modeling Simulation Setup and Methodsmentioning

confidence: 99%

Modeling stem cell nucleus mechanics using confocal microscopy

Kennedy

Newberg

Goelzer

et al. 2020

Preprint

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Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells (MSC) were converted into finite element models and siRNA-mediated LaminA/C depletion isolated chromatin and LaminA/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and LaminA/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests.

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

Cited by 17 publications

References 54 publications

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

Modeling stem cell nucleus mechanics using confocal microscopy

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