Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297328 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mesenchymal stem cells (MSCs) participate in the repair/remodeling of many tissues, where MSCs commit to different lineages dependent on the cues in the local microenvironment. Here we show that TGFβ-activated RhoA/ROCK functions as a molecular switch regarding the fate of MSCs in arterial repair/remodeling after injury. MSCs differentiate into myofibroblasts when RhoA/ROCK is turned on, endothelial cells when turned off. The former is pathophysiologic resulting in intimal hyperplasia, whereas the latter is physiological leading to endothelial repair. Further analysis revealed that MSC RhoA activation promotes formation of an extracellular matrix (ECM) complex consisting of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). Inactivation of RhoA/ROCK in MSCs induces matrix metalloproteinase-3-mediated CTGF cleavage, resulting in VEGF release and MSC endothelial differentiation. Our findings uncover a novel mechanism by which cell-ECM interactions determine stem cell lineage specificity and offer additional molecular targets to manipulate MSC-involved tissue repair/regeneration.
2016-03-01 | GSE73557 | GEO
Project description:Mesenchymal stem cells (MSCs) participate in the repair/remodeling of many tissues, where MSCs commit to different lineages dependent on the cues in the local microenvironment. Here we show that TGFβ-activated RhoA/ROCK functions as a molecular switch regarding the fate of MSCs in arterial repair/remodeling after injury. MSCs differentiate into myofibroblasts when RhoA/ROCK is turned on, endothelial cells when turned off. The former is pathophysiologic resulting in intimal hyperplasia, whereas the latter is physiological leading to endothelial repair. Further analysis revealed that MSC RhoA activation promotes formation of an extracellular matrix (ECM) complex consisting of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). Inactivation of RhoA/ROCK in MSCs induces matrix metalloproteinase-3-mediated CTGF cleavage, resulting in VEGF release and MSC endothelial differentiation. Our findings uncover a novel mechanism by which cell-ECM interactions determine stem cell lineage specificity and offer additional molecular targets to manipulate MSC-involved tissue repair/regeneration. Mouse bone marrow MSCs were purchased from Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine. All MSCs were cultured in αMEM supplied with 10% FCS. The transfection of DNA plasmids were performed with Lipofectamine® LTX with Plus Reagent (Life Technologies). Myc-L63RhoA or empty vector (control) was transfected into mouse bone marrow MSCs. Three days later, the cells were harvested and total RNA was isolated using RNeasy Mini kit (Qiagen). A total of four independent experiments were performed. RNA samples were assessed for quality and integrity using Synergy HT (Biotek, Winooski, VT). Microarray expression profiles were generated using the Illumina MouseRef-8 v2.0 Expression BeadChip (Illumina, San Diego, CA). Biotin-labeled cRNA was synthesized by the total prep RNA amplification kit from Ambion (Austin, TX). cRNA was quantified and normalized to 75 ng/µl, and then 1µg was hybridized to Beadchips. The hybridized chip was scanned using the Illumina iScan system and background corrected signal intensities were extracted using the GenomeStudio software (Illumina). The lumi R package was used to transform the data using a Variance Stabilizing Transformation (VST) and normalized using quantile normalization. Differential expression analysis was performed using the R/Mannova package. P-values were calculated by performing 1000 permutations, then corrected for multiple comparisons by false-discovery rate (FDR) transformation, using a 20% FDR cutoff.
2016-03-01 | E-GEOD-73557 | biostudies-arrayexpress
Project description:Biomaterials engineered to mimic extracellular matrix (ECM) topography play a pivotal role in tissue engineering. Previous research indicates that certain biomimetic topographies can guide stem cells towards multiple specific lineages. However, the mechanisms by which these topographic cues prime the multilineage differentiation remain largely elusive. In this study, we show that topography influences nuclear tension in MSCs through a mechanotransductive feedback mechanism, which in turn reshapes chromatin accessibility patterns, finally determines the stem cell lineage commitment. When cultured on an aligned substrate, MSCs show high cytoskeletal tension along the fibre direction, resulting in anisotropic nucleus tensile stress. This further leads to the opening of chromatin sites related to neurogenic, myogenic, and tenogenic genes by the regulation of transcription factors such as TLX. On the other hand, when MSCs are lied on a random substrate, they experience isotropic nucleus stress, leading to the opening of chromatin sites related to osteogenic and chondrogenic genes through the regulation of RUNX family transcription factors. Collectively, our results show that aligned and random topography induce site specific chromatin stretching and lineage specific gene expressing in MSCs, leading to their priming for specific lineages. Our study thus proposes a novel concept for topographic cues influencing on cell behavior and fate during tissue reconstitution and regeneration.
2024-12-25 | GSE263530 | GEO
Project description:Biomaterials engineered to mimic extracellular matrix (ECM) topography play a pivotal role in tissue engineering. Previous research indicates that certain biomimetic topographies can guide stem cells towards multiple specific lineages. However, the mechanisms by which these topographic cues prime the multilineage differentiation remain largely elusive. In this study, we show that topography influences nuclear tension in MSCs through a mechanotransductive feedback mechanism, which in turn reshapes chromatin accessibility patterns, finally determines the stem cell lineage commitment. When cultured on an aligned substrate, MSCs show high cytoskeletal tension along the fibre direction, resulting in anisotropic nucleus tensile stress. This further leads to the opening of chromatin sites related to neurogenic, myogenic, and tenogenic genes by the regulation of transcription factors such as TLX. On the other hand, when MSCs are lied on a random substrate, they experience isotropic nucleus stress, leading to the opening of chromatin sites related to osteogenic and chondrogenic genes through the regulation of RUNX family transcription factors. Collectively, our results show that aligned and random topography induce site specific chromatin stretching and lineage specific gene expressing in MSCs, leading to their priming for specific lineages. Our study thus proposes a novel concept for topographic cues influencing on cell behavior and fate during tissue reconstitution and regeneration.
2024-12-25 | GSE263529 | GEO
Project description:Extracellular signals and cell-fate trajectories during vein development remain elusive, despite trailblazing insights into artery development. Here we exploit human pluripotent stem cell differentiation and mouse embryology to present a model that answers longstanding questions: vein endothelial cell (EC) differentiation unfolds in two steps driven by opposing extracellular signals. First, VEGF differentiates mesoderm into “primed” ECs, newly-defined progenitors that co-express certain arterial (SOX17) and venous (APLNR) markers. Second, primed ECs execute vein differentiation upon VEGF/ERK inhibition; however, upon VEGF activation they can instead form artery ECs. The arteriovenous plasticity of primed ECs was supported by intersectional lineage tracing. Future venous genes including NR2F2 harbor poised chromatin in primed ECs, but are only transcribed upon VEGF/ERK inhibition. SOXF transcription factors, including SOX17, confer primed ECs with vein differentiation competence. Collectively, this two-step vein differentiation model—entailing primed EC intermediates and VEGF/ERK inhibition to trigger vein differentiation—has implications for VEGF-modulating therapies.
2026-04-06 | GSE326938 | GEO
Project description:Extracellular signals and cell-fate trajectories during vein development remain elusive, despite trailblazing insights into artery development. Here we exploit human pluripotent stem cell differentiation and mouse embryology to present a model that answers longstanding questions: vein endothelial cell (EC) differentiation unfolds in two steps driven by opposing extracellular signals. First, VEGF differentiates mesoderm into “primed” ECs, newly-defined progenitors that co-express certain arterial (SOX17) and venous (APLNR) markers. Second, primed ECs execute vein differentiation upon VEGF/ERK inhibition; however, upon VEGF activation they can instead form artery ECs. The arteriovenous plasticity of primed ECs was supported by intersectional lineage tracing. Future venous genes including NR2F2 harbor poised chromatin in primed ECs, but are only transcribed upon VEGF/ERK inhibition. SOXF transcription factors, including SOX17, confer primed ECs with vein differentiation competence. Collectively, this two-step vein differentiation model—entailing primed EC intermediates and VEGF/ERK inhibition to trigger vein differentiation—has implications for VEGF-modulating therapies.
2026-04-06 | GSE326936 | GEO
Project description:Extracellular signals and cell-fate trajectories during vein development remain elusive, despite trailblazing insights into artery development. Here we exploit human pluripotent stem cell differentiation and mouse embryology to present a model that answers longstanding questions: vein endothelial cell (EC) differentiation unfolds in two steps driven by opposing extracellular signals. First, VEGF differentiates mesoderm into “primed” ECs, newly-defined progenitors that co-express certain arterial (SOX17) and venous (APLNR) markers. Second, primed ECs execute vein differentiation upon VEGF/ERK inhibition; however, upon VEGF activation they can instead form artery ECs. The arteriovenous plasticity of primed ECs was supported by intersectional lineage tracing. Future venous genes including NR2F2 harbor poised chromatin in primed ECs, but are only transcribed upon VEGF/ERK inhibition. SOXF transcription factors, including SOX17, confer primed ECs with vein differentiation competence. Collectively, this two-step vein differentiation model—entailing primed EC intermediates and VEGF/ERK inhibition to trigger vein differentiation—has implications for VEGF-modulating therapies.
2026-04-06 | GSE326989 | GEO
Project description:An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion (fig. 1). Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.
2020-10-22 | PXD021539 | Pride
Project description:mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs. Bone marrow-derived MSCs were stably transduced with lentivirus expressing CTGF-specific shRNA or an empty vector control. After antibiotic selection, total RNA was amplified and hybridized to Illumina HT12 version 3 human whole-genome arrays (Illumina, San Diego, CA).
2013-08-05 | E-GEOD-47575 | biostudies-arrayexpress
Project description:mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
2013-08-05 | GSE47575 | GEO