Project description:To investigate how histone demethylases KDM4B and KDM6B may be involved in osteogenic commitment of mesenchymal stem cells (MSCs), we performed gene expression profiling and comparison on control, KDM4B- and KDM6B-knockdown MSCs at different stages of osteogenic differentiation. Human MSCs infected with scramble shRNAs, shRNAs against KDM4B or KDM6B are treated with BMP4/7 for 0, 4 and 24hrs. Total RNA were extracted from these 9 samples.
Project description:To investigate how histone demethylases KDM4B and KDM6B may be involved in osteogenic commitment of mesenchymal stem cells (MSCs), we performed gene expression profiling and comparison on control, KDM4B- and KDM6B-knockdown MSCs at different stages of osteogenic differentiation.
Project description:Global gene expression data of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture onto osteoinductive scaffolds in perfusion bioreactors. The hypothesis tested in the present study was that perfusion culture in bioreactors influenced the expression levels of several genes involved in proliferation and osteogenic differentiation. Results provide important information of the response of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cell to osteogenic stimulation under perfusion cultures, such as genes involved in cell proliferation and division as well as osteogenic differentiation and bone development. Total RNA obtained from human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture under osteogenic conditions in perfusion bioreactors for 5 weeks.
Project description:In this study, we identify histone demethylase KDM6B as a critical regulator of osteogenic differentiation in mechanically stimulated periodontal ligament stem cells (PDLSCs). Prior sequencing initiatives and research have underscored KDM6B's mechanosensitivity and illuminated how advanced glycation end-products (AGEs) inhibit KDM6B, thereby impairing stem cell differentiation capabilities. Significant H3K27Me3 enrichment was observed at the transcriptional regions of osteogenic markers (ALP, RUNX2, BMP2, COL1A1) in pluripotent stem cells, with KDM6B essential for the demethylation of H3K27Me3. Moreover, KDM6B was found to activate several critical genes within both the canonical and non-canonical Wnt pathways, enhancing TCF and NFATC family gene expression and facilitating antioxidative responses, matrix adhesion, and intercellular interactions in PDLSCs. Collectively, our data establish a molecular framework that illustrates the cooperative role of lineage-specific histone modifiers in osteogenic differentiation, highlights KDM6B's function in eradicating repressive histone marks, and delineates a reciprocal enhancement loop involving KDM6B and the Wnt signaling pathways.
Project description:Ability to perform osteogenic differentiation is one of the minimal criteria of mesenchymal stem cells (MSCs). Still, it is generally unknown whether osteogenic differentiation is universal cell fate or various phenotypically similar cell states. Besides this, MSCs and their secretomes are actively using for cell/cell-free therapy development, but systemic inter-source variation in MSCs secretomes, proteomes and differentiation mechanisms are still poorly understood. Therefore, here we compared proteomic and secretomic profiles of human mesenchymal cells from six sources: osteoblasts (bone), WJ-MSCs (Warton’s jelly), AD-MSCs (adipose), PDLSCs (tooth: Periodontal Ligament Stem Cells), DPSCs (tooth: Dental Pulp Stem Cells) and GFs (tooth: Gingival Fibroblasts). For experiments we used cells in early passages (3-5) isolated from 3-6 individuals. All cells were compared in standard cultivation and in the 10th day after induction of osteogenic differentiation.
Project description:Global gene expression data of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture onto osteoinductive scaffolds in perfusion bioreactors. The hypothesis tested in the present study was that perfusion culture in bioreactors influenced the expression levels of several genes involved in proliferation and osteogenic differentiation. Results provide important information of the response of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cell to osteogenic stimulation under perfusion cultures, such as genes involved in cell proliferation and division as well as osteogenic differentiation and bone development.
Project description:bFGF regulated stemness maintenance and cell differentiation in stem cells isolated from human exfoliated deciduous teeth (SHEDs). In addition, WNT3A is also shown to regulate osteogenic differentiation in mesenchymal stem cells. Here, transcriptome analysis of bFGF and WNT3A treated SHEDs was evaluated using a high throughput RNA sequencing technique. Results demonstrated that bFGF regulated genes related to cell cycle control and cell proliferation in SHEDs.
Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.
Project description:Bone-mesenchymal stem cells (MSCs) reside in a hypoxic niche that maintains their differentiation potential. Although the role of hypoxia (low oxygen concentration) in the regulation of stem cell function has been previously reported, with normoxia (high oxygen concentration) leading to impaired osteogenesis, the molecular events triggering changes in stem cell fate decisions in response to high oxygen remain elusive. Here, we study the impact of normoxia on the mito-nuclear communication with regards to stem cell differentiation. We show that normoxia-cultured MSCs undergo profound transcriptional alterations which cause irreversible osteogenesis defects. Mechanistically, high oxygen promotes chromatin compaction and histone hypo-acetylation, particularly on promoters and enhancers of osteogenic genes. Although normoxia induces metabolic rewiring resulting in high acetyl-CoA levels, histone hypo-acetylation occurs due to trapping of acetyl-CoA inside mitochondria, owing to lower CiC activity. Strikingly, restoring the cytosolic acetyl-CoA pool remodels the chromatin landscape and rescues the osteogenic defects. Collectively, our results demonstrate that the metabolism-chromatin-osteogenesis axis is heavily perturbed in response to high oxygen and identify CiC as a novel, oxygen-sensitive regulator of the MSC function.