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Effect of microtopography-induced nuclear constriction on chromatin accessibility and gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224265 | GEO | 2023/02/04

REPOSITORIES: GEO

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Effect of microtopography-induced nuclear constriction on chromatin accessibility in mesenchymal stromal cells in growth and osteogenic differentiation conditions.

Project description:To investigate the influence of microtopography-induced constriction of cell nuclei on chromatin accessibility and gene expression in human mesenchymal stromal cells (hMSCs)

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Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions II

Project description:To investigate the influence of microtopography-induced constriction of cell nuclei on gene expression in human mesenchymal stromal cells (hMSCs)

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Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions I

Project description:To investigate the influence of microtopography-induced constriction of cell nuclei on gene expression in human mesenchymal stromal cells (hMSCs)

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Effect of microtopography-induced nuclear constriction on chromatin accessibility in mesenchymal stromal cells in growth and osteogenic differentiation conditions.

Project description:Effect of microtopography-induced nuclear constriction on chromatin accessibility in mesenchymal stromal cells in growth and osteogenic differentiation conditions.

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AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth.

Project description:Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34+ or CD33+ cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs. Gene expression array analysis revealed that AML cells induce connective tissue growth factor (CTGF) expression in BM-MSCs irrespective of AML type. Overexpression of CTGF in a transgenic mouse model greatly enhanced leukemia engraftment in vivo. Together, our data suggest that AML cells induce a preosteoblast-rich niche in the BM that in turn enhances AML expansion.

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Effect of microtopography-induced nuclear constriction on chromatin accessibility and gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions

Project description:Effect of microtopography-induced nuclear constriction on chromatin accessibility and gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions

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Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells.

Project description:The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 μm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving α2 and α5 integrins. Further silencing either α2 or α5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the α2 and α5 integrins as mechano-sensitive molecules mediate MSCs' ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues.

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Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions I

Project description:Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions I

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Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions II

Project description:Effect of microtopography-induced nuclear constriction on gene expression in mesenchymal stromal cells in growth and osteogenic differentiation conditions II

| PRJNA930424 | ENA

Effect of low-magnitude, high-frequency vibration on osteogenic differentiation of rat mesenchymal stromal cells.

Project description:Whole body vibration (WBV), consisting of a low-magnitude, high-frequency (LMHF) signal, is anabolic to bone in vivo and may act through alteration of the lineage commitment of mesenchymal stromal cells (MSC). We investigated the effect of LMHF vibration on rat bone marrow-derived MSCs (rMSCs) in an in vitro system. We subjected rMSCs to repeated (six) bouts of 1-h vibration at 0.3g and 60?Hz in the presence of osteogenic (OS) induction medium. The OS differentiation of rMSCs under the loaded and non-loaded conditions was assessed by examining cell proliferation, alkaline phosphatase (ALP) activity, mRNA expression of various osteoblast-associated markers [ALP, Runx2, osterix (Osx), collagen type I alpha 1 (COL1A1), bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN)], and matrix mineralization. LMHF vibration did not enhance the OS differentiation of rMSCs. Surprisingly, the mRNA level of Osx, a transcription factor necessary for osteoblast formation, was decreased, and matrix mineralization was inhibited. Our findings suggest that LMHF vibration may exert its anabolic effects in vivo via mechanosensing of a cell type different from MSCs.

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