Project description:Expression profile of dermal fibroblasts reprogrammed to a pluripotent state Experiment Overall Design: Compared fibroblasts to reprogrammed fibroblasts to human ES cells
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.
Project description:Induced cellular reprogramming to the pluripotent state offers a novel stem cell source for autologous transplantation. While recent studies have explored the role of factors required for induced pluripotent stem cell (iPSC) induction, the cellular and molecular basis of reprogramming from human fibroblasts remains elusive. Here, we have identified a subset of human dermal-derived fibroblasts that shares hallmark molecular and epigenetic features with pluripotent cells. Functional studies demonstrate that these cells contribute to the majority of human iPSCs generated from dermal fibroblasts and are dependent on heterogeneous fibroblast microenvironment for reprogramming competency. Molecular characterization indicated these predisposed fibroblasts were unique to other dermal derived stem cells and possessed features of proliferative selfrenewal. Our study reveals human fibroblasts are not equivalently capable of cellular reprogramming, and suggests that reprogramming factors overcome commitment steps that allow predetermined dermal fibroblasts to establish stable pluripotent state.
Project description:Transcriptional profiling of reprogrammed cells at day 20 post-transduction comparing compact and differentiated colonies with established induced Pluripotent Stem Cells (iPSC) generated from human dermal fibroblasts (HDF). This study focused in the identification of upregulated transcription factors related to early developmental processes, particularly during primitive streak formation.
Project description:We describe a so far uncharacterized, embryonic and self-renewing Neural Plate Border Stem Cell (NBSC) population with the capacity to differentiate into central nervous and neural crest lineages. NBSCs can be obtained by neural transcription factor-mediated reprogramming (BRN2, SOX2, KLF4, and ZIC3) of human adult dermal fibroblasts and peripheral blood cells (induced Neural Plate Border Stem Cells, iNBSCs) or by directed differentiation from human induced pluripotent stem cells (NBSCs). Moreover, human (i)NBSCs share molecular and functional features with an endogenous NBSC population isolated from neural folds of E8.5 mouse embryos. Upon differentiation, iNBSCs give rise to either (1) radial glia-type stem cells, dopaminergic and serotonergic neurons, motoneurons, astrocytes, and oligodendrocytes or (2) cells from the neural crest lineage. Here we provide array-based methylation data of iNBSCs reprogrammed from adult dermal fibroblasts (ADF), iPSC-derived NBSCs and adult dermal fibroblasts. The data provided demonstrate robust changes in the methylation landscape after reprogramming of human adult dermal fibroblasts into iNBSCs.