Project description:Nephritis (LN) is a serious manifestation of SLE. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these models. In this study we used an unbiased transcriptional network approach to define similarities and differences between three lupus models and human LN. Affymetrix-based expression profiles were analyzed using Genomatix Bibliosphere software and transcriptional networks were compared using the Tool for Approximate LargE graph matching (TALE). The 20 network hubs (nodes) shared between all three models and human LN reflect key pathologic processes, namely immune cell infiltration/activation, macrophage/dendritic cell activation, endothelial cell activation/injury and tissue remodeling/fibrosis. Each model also shares unique features with human LN. Pathway analysis of the TALE nodes highlighted macrophage/DC activation as a cross-species shared feature. To distinguish which genes and activation pathways might derive from mononuclear phagocytes in the human kidneys the gene expression profile of isolated NZB/W renal mononuclear cells was compared with human LN kidney profiles. Network analysis of the shared signature highlighted NFkappaB1 and PPARgamma as major hubs in the tubulointerstitial and glomerular networks respectively. Key nodes in the renal macrophage inflammatory response form the basis for further mechanistic and therapeutic studies. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with lupus nephritis (LN) RNA from glomeruli and tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix microarrays.
Project description:A fully defined media for human embryonic stem cells (hESCs) was designed after examining the phosphorylation status of 42 receptor tyrosine kinases (RTKs) on hESCs exposed to mouse embryonic fibroblast conditioned medium (CM). Activation of the insulin and insulin-like growth factor-1 receptors (IR, IGF1R) as well as EGFR family members including ERBB2 and ERBB3 led to the design of a simple defined media which supported robust long-term growth of multiple hESC lines and allowed massive expansion of undifferentiated cells. Illumina bead arrays were used to demonstrate the maintenance of gene expression profiles characteristic of pluripotent cells in cultures grown in CM or defined media. Keywords: Comparison of cells in different culture conditions
Project description:Nephritis (LN) is a serious manifestation of SLE. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these models. In this study we used an unbiased transcriptional network approach to define similarities and differences between three lupus models and human LN. Affymetrix-based expression profiles were analyzed using Genomatix Bibliosphere software and transcriptional networks were compared using the Tool for Approximate LargE graph matching (TALE). The 20 network hubs (nodes) shared between all three models and human LN reflect key pathologic processes, namely immune cell infiltration/activation, macrophage/dendritic cell activation, endothelial cell activation/injury and tissue remodeling/fibrosis. Each model also shares unique features with human LN. Pathway analysis of the TALE nodes highlighted macrophage/DC activation as a cross-species shared feature. To distinguish which genes and activation pathways might derive from mononuclear phagocytes in the human kidneys the gene expression profile of isolated NZB/W renal mononuclear cells was compared with human LN kidney profiles. Network analysis of the shared signature highlighted NFkappaB1 and PPARgamma as major hubs in the tubulointerstitial and glomerular networks respectively. Key nodes in the renal macrophage inflammatory response form the basis for further mechanistic and therapeutic studies. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with lupus nephritis (LN)
Project description:Bulk RNA sequencing of sorted peri-pancreatic LN cDC1s from different stages of neoplastic development in the KPC mouse model of pancreatic adenocarcinoma.
Project description:22 patients with IDC: 8 without LN metastases (IDC) and 14 with sentinel LN metastases (IDCM). Sampling was limited to 29 paraffin blocks which could be used up without interference with diagnostic procedures: 8 IDCs, 11 IDCMs and 10 ipsilateral LN metastases [5 to the sentinel LN (first in lymph drainage chain, MS) and 5 to more distal (MD)]. 7 IDCMs had samples of their LN metastases (IDCM9,13, 14, 15, 17, 18, 19). 3 samples of metastases (MS20, 21, 22) did not have paired primary IDCM samples and 4 IDCMs (IDCM10, 11, 12, 16) did not have samples of their LN metastases. Keywords: Comparative clinical study