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
View SamplesPatients with Klinefelter Syndrome have the karyotype 47,XXY. These men are suffering from hypergonadotropic hypogonadism and are infertile. It is debated whether the different hormonal constitution observed in these patients or different gene expression
Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome.
Sex, Specimen part
View SamplesExpression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
Specimen part
View SamplesGene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes.
Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.
No sample metadata fields
View SamplesConrad et al. Nature 456, 344349 (2008) have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comparing the expression of pluripotency marker genes in haGSCs and hESCs, and in haGSCs and human fibroblast samples derived from different laboratories, including our own. We find that haGSCs and fibroblasts have a similar gene-expression profile, but that haGSCs and hESCs do not. The pluripotency of Conrad and colleagues haGSCs is therefore called into question.
Human adult germline stem cells in question.
Specimen part
View SamplesKnockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells.
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Specimen part, Disease, Disease stage, Treatment
View SamplesRats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
No sample metadata fields
View SamplesBP and ER encode proteins that act synergistically to regulate Arabidopsis inflorescence architecture. To search for genes/proteins that influence the BP/ER signaling pathways, we conducted mutagenesis of the bp er double mutant and found that a mutation in FILAMENTOUS FLOWER (FIL) suppresses many of the morphological/developmental defects in bp er. Given that FIL encodes a Zn-finger containing transcription factor, microarray analysis was conducted on bp er vs. the bp er fil line to identify genes that are misregulated and which might implicate specific genes/proteins/pathways that are involved in regulating inflorescence development.
A novel Filamentous Flower mutant suppresses brevipedicellus developmental defects and modulates glucosinolate and auxin levels.
No sample metadata fields
View SamplesTime and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
No sample metadata fields
View SamplesBromodomain and extra terminal domain (BET) inhibition reduces occupancy of BET-family proteins at promoter and enhancer sites resulting in changes in the transcription of specific genes.
Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS-mutated NSCLC to pro-apoptotic agents.
Specimen part, Cell line
View Samples