Project description:Human mesenchymal stem cells (hMSC) have an extensive potential for clinical applications in cell therapy. However, very little is known of the specific molecular regulatory mechanisms that control the therapeutical properties of these cells. We aimed to identify microRNAs (miRNAs) that could be involved in controlling the transition between the self-renewing (undifferentiated) and the reparative (differentiated) phenotypes of hMSCs. MicroRNA microarrays were used to identify miRNAs that are upregulated in undifferentiated hMSCs. For that, we compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of in vitro adipogenic or osteogenic induction. We also compared the miRNA expression profiles of undifferentiated hMSCs with skin fibroblasts (a mesenchymal cell lineage with a more restricted differentiation potential). These experiments allowed us to identify miR-335 as the only miRNA downregulated upon MSC differentiation as well as in MSCs in comparison with skin fibroblasts. Gene expression microarrays were used to identify genes that are downregulated in hMSCs overexpressing miR-335. We compared the miRNA expression profiles of hMSCs transduced with a lentiviral vector encoding miR-335 with MSCs transduced with a control lentiviral vector. Our results suggest miR-335 downregulation could be a critical trigger for the initiation of MSCs activities involved in tissue repair and remodelling, including cell proliferation, migration and differentiation.
Project description:Human mesenchymal stem cells (hMSC) have an extensive potential for clinical applications in cell therapy. However, very little is known of the specific molecular regulatory mechanisms that control the therapeutical properties of these cells. We aimed to identify microRNAs (miRNAs) that could be involved in controlling the transition between the self-renewing (undifferentiated) and the reparative (differentiated) phenotypes of hMSCs. MicroRNA microarrays were used to identify miRNAs that are upregulated in undifferentiated hMSCs. For that, we compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of in vitro adipogenic or osteogenic induction. We also compared the miRNA expression profiles of undifferentiated hMSCs with skin fibroblasts (a mesenchymal cell lineage with a more restricted differentiation potential). These experiments allowed us to identify miR-335 as the only miRNA downregulated upon MSC differentiation as well as in MSCs in comparison with skin fibroblasts. Gene expression microarrays were used to identify genes that are downregulated in hMSCs overexpressing miR-335. We compared the miRNA expression profiles of hMSCs transduced with a lentiviral vector encoding miR-335 with MSCs transduced with a control lentiviral vector. Our results suggest miR-335 downregulation could be one of the triggers for the initiation of MSCs activities involved in tissue repair and remodelling, including cell migration and differentiation. We compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of adipogenic or osteogenic induction, as well as with skin fibroblasts. A total of four independent samples were used for each condition. For the adipogenic/osteogenic vs. undifferentiated MSC comparison, the RNA samples were pooled (two independent samples/pool) before labeling. We also compared the miRNA expression profiles of hMSCs transduced with the lentiviral vector pLV-EmGFP-MIRN335 with MSCs transduced with the control vector pLV-EmGFP-Mock. For the gene expression microarrays, a total of three independent samples were used for each condition.
Project description:Analysis of human mesenchymal stem cells (MSC) from bone marrow and the Wharton's jelly of the umbilical cord after manupulating miR-146a-5p expression. miR-146a-5p is involved in controlling the proliferation and migration of MSCs. Results provide miR-146a-5p-regulating genes in MSCs.
Project description:We developed a compartmental model of the small intestinal epithelium that describes stem and progenitor cell proliferation and differentiation and cell migration onto the villus. The model includes a negative feedback loop from villus cells to regulate crypt proliferation and integrates heterogeneous epithelial-related processes, such as the transcriptional profile, citrulline kinetics and probability of diarrhea.
Project description:Recent development of integrative therapy against melanoma combines surgery, radiotherapy, targeted therapy, and immunotherapy; however, the clinical outcomes of advanced stage and recurrent melanoma are poor. As a skin cancer, melanoma is generally resistant to radiotherapy. Hence, there is an urgent need for evaluation of the mechanisms of radioresistance. The present study identified miR-335 as one of the differential expression of miRNAs in recurrent melanoma biopsies post-radiotherapy. The expression of miR-335 declined in melanoma tissues compared to the adjacent tissues. Moreover, miR-335 expression correlated with advanced stages of melanoma negatively. Consistent with the prediction of STARBASE and miRDB database, miR-335 targeted ROCK1 via binding with 3’-UTR of ROCK1 directly, resulting in attenuation of proliferation, migration and radioresistance of melanoma cells. The authors validated that overexpression of miR-335 enhanced X-ray-induced tumor regression by B16 mouse models. Briefly, the present findings gained insights into miR-335/ROCK1-mediated radiosensitivity and provided a promising therapeutic strategy for improving radiotherapy against melanoma. miRNAs profiling by array
Project description:Analysis of human mesenchymal stem cells (MSC) from bone marrow and the Wharton's jelly of the umbilical cord after manupulating miR-146a-5p expression. miR-146a-5p is involved in controlling the proliferation and migration of MSCs. Results provide miR-146a-5p-regulating genes in MSCs. In this study, BM-MSCs transduced with miR-146a-5p expression vector or pCDH-CMV-MCS-EF1-copGFP vector only, as well as two WJ-MSCs transfected with short interfering RNAs targeting miR-146a or a GFP control.
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:The proliferation, migration, and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) play vital roles in maintaining bone mass and metabolism. BMSC base cell therapy has become a competitive treatment option for osteoporosis.Small are critical regulators of cellular processes. Small RNA sequencing was used to detect piRNA expression during BMSC proliferation.
Project description:We developed a strategy to generate cardiac progenitor cells from human induced pluripotent stem cells using a novel small molecule.miRNA-sequencing results showed different miRNA expression profile among undifferentiated human induced pluripotent stem cells(hiPSCs), DMSO and ISX-9 treated hiPSCs.In comparsion with DMSO treated cells, ISX-9 upregulated several myogenic miRNAs and cardiac hypertrophy related-miRNAs including miR-335, miR-21, miR-30c,miRNA-181a and miR-214.