Background: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. Methods: The two lineages are prospectively isolated by FACS based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase stained cultures. Results: Lobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Conclusions: Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.
Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.
Specimen part
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Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Specimen part
View SamplesThe object of this study was to investigate the effect of elevated glucose concentrations (15 and 25 mM glucose) on gene expression in undifferentiated and adipogenic differentiated ASCs.
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Specimen part
View SamplesThe aim of this study was to characterize basal gene expression for proliferating adipose tissue MSCs, cultured at normal cell culture conditions.
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Specimen part
View SamplesMastitis in dairy cows is one of the most costly and prevalent diseases affecting dairy cows world wide. Insight in the molecular regulation of the host immune response to an E. coli infection, could help to develop new strategies to prevent cattle from E. coli infection. Here we performed a gene-expression analysis from udder tissue exposed to a controlled E. coli infection at T=24h post infection (p.i.) representing the acute phase response and at T=192h p.i. representing a chronic stage.
In depth analysis of genes and pathways of the mammary gland involved in the pathogenesis of bovine Escherichia coli-mastitis.
Specimen part, Treatment
View SamplesLiver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
No sample metadata fields
View SamplesWe studied the response to infection and associated perturbations to the bovine livers normal function by examining gene transcription data from liver biopsies collected following an E. coli infection in the udder of primiparous dairy cows. This is the first study to examine gene transcription responses to systemic infection by the E. coli bacterium in dairy cows. First, we verified that the inoculation protocol resulted in systemic infection in the cows. This was done based on records on three clinical symptoms: body temperature and amount of E. coli bacteria and leukocytes in milk samples. Second, we examined gene transcription patterns underlying the clinical traits. Gene transcription levels at times of peak values for the clinical traits were estimated in the liver to study indications of an acute phase response to systemic E. coli infection in the cows. Finally, we compared gene transcription responses to E. coli infection and lipopolysaccaride (LPS) inoculation.
Transcriptional profiling of the bovine hepatic response to experimentally induced E. coli mastitis.
Sex, Specimen part, Time
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