Project description:Comparison of gene expression profiles in three samples of normal human atrial cardiac fibroblasts, normal human ventricular cardiac fibroblasts, normal human dermal fibroblasts, human bone marrow-derived mesenchymal stem cells and human iPS cell-derived fibroblasts using microarray analysis.
Project description:Identification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa. Affymetrix microarrays were used to define differential gene expression. Populations of fibroblasts were isolated from human normal oral mucosa, oral dysplasia and oral squamous cell carcinoma, maintained in 3D collagen I biomatrices, RNA extracted and processed for Affymetrix arrays. Fibroblasts maintained as monolayers were also included as comparators.
Project description:To define the characteristics of human oral mucosa fibroblasts (hOFs), we analyzed the gene expression of hOFs compared with that of human dermal fibroblasts (hDFs), and that of hOF-derived induced pluripotent stem cells (hOF-iPSCs). In this dataset, we found that 5,738 probes and 5672 probes were differently expressed in hOFs and hDFs respectively, compared with those in hOF-iPSCs at more than 2-fold levels. In contrast, only 434 probes are differently expressed between hOFs and hDFs.
Project description:Identification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa. Affymetrix microarrays were used to define differential gene expression.
Project description:Genetically matched human iPSCs from different origins were generated using bone marrow stromal cells and dermal fibroblasts of the same donor, and the global gene expression profile were analyzed. Comparison of gene expressions among 14 iPS clones, 4 and 4 were derived from bone marrow stromal cells(BM), 2 and 4 were from dermal skin fibroblasts(SF) of donor90 and 91, respectively.
Project description:Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J? in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Examination of genome-wide CSL binding sites in primary human dermal fibroblasts usinf two different antibodies against CSL
Project description:Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-Jκ in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.
