The immortalized human urothelial cell line, UROtsa, was transformed in six parallel cultures with continual passaging in1 M Cd+2 until the cells were able to attain the ability to form colonies in soft agar and subcutaneous tumors in nude mice. The gene expression profiles between cadmium-transformed and control samples were compared and the differentially expressed genes were identified.
Variation of keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells (UROtsa).
Cell line
View SamplesMesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1M) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1M and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells.
Specimen part
View SamplesBone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Specimen part, Subject
View SamplesLgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into 3D epithelial organoids containing all cell types at nearnormal ratios. Culture conditions to generate the main cell types have been established previously, but signals inducing the various types of enteroendocrine cells (EECs) have remained elusive. Here we generate quiescent Lgr5+ stem cells in vitro by inhibition of the EGF-receptor (EGFR) and mitogen-associated protein kinase (MAPK) signaling pathways in organoids, a state that can be readily reversed. Quiescent Lgr5+ stem cells gain a distinct molecular signature, biased towards EEC differentiation. Indeed, combined inhibition of Wnt, Notch and MAPK pathways efficiently generates a diversity of EEC subtypes in vitro. Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and cell fate choice, and provide an in vitro approach for the study of the elusive EECs. Overall design: We established a stable culture of quiescent Lgr5+ intestinal stem cells in culture. These highly resemble quiescent secretory precursors, which has high EEC differentiation potential. Following on this lead, we elucidated what signals are required to generate EEC cells of all varieties, and provide a method to produce these EEC cells in large numbers.
Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells.
Specimen part, Cell line, Subject
View SamplesActing downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. In vivo imaging identified two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activity depended on ErbB2 and EGFR, respectively. Notably, deregulated activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augmented EGFR signalling and exalted it to a dominant driver of ERK activity dynamics, which rendered IECs addicted to EGFR signalling. Furthermore, the frequency of ERK activity pulses was also increased to promote cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations underlie tumour-specific sensitivity to pharmacological EGFR inhibition. In this microarray analysis, we aimed to elucidate molecular mechanisms that mediate Wnt signalling activation-induced alterations in EGFR-ERK signalling dynamics.
Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.
Specimen part
View SamplesWe have studied the plasma membrane protein phenotype of human culture-amplified and native Bone Marrow Mesenchymal Stem Cells (BM MSCs). We have found, using microarrays and flow cytometry, that cultured cells express specifically 113 transcripts and 17 proteins that were not detected in hematopoietic cells. These antigens define a lineage-homogenous cell population of mesenchymal cells, clearly distinct from the hematopoietic lineages, and distinguishable from other cultured skeletal mesenchymal cells (periosteal cells and synovial fibroblasts). Among the specific membrane proteins present on cultured MSCs, 9 allowed the isolation from BM mononuclear cells of a minute population of native MSCs. The enrichment in Colony-Forming Units-Fibroblasts was low for CD49b, CD90 and CD105, but high for CD73, CD130, CD146, CD200 and integrin alphaV/beta5. Additionally, the expression of CD73, CD146 and CD200 was down-regulated in differentiated cells. The new marker CD200, because of its specificity and immunomodulatory properties, deserves further in depth studies.
Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells.
Sex, Age, Specimen part, Treatment
View SamplesIn a screen for upregulated adipocyte genes in insulin resistant versus insulin sensitive subjects matched for BMI, we identified the type II transmembrane protein tenomodulin (TNMD), previously implicated in glucose tolerance in gene association studies. TNMD expression was greatly increased in human preadipocytes during differentiation, while silencing TNMD blocked adipogenic gene induction and adipogenesis.
Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
Specimen part
View SamplesThis is a whole transcriptome sequencing data of rat testis. YY1 gene was knocked down in Experimental animals under Sertoli cell specific and puberty specific promoter. These knockdown animals were compared with the control animals.
An integrated transcriptomics-guided genome-wide promoter analysis and next-generation proteomics approach to mine factor(s) regulating cellular differentiation.
No sample metadata fields
View SamplesThe epidemic character of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring -lactam antibiotic class resistance and a putative pathogenicity island, ACME (arginine catabolic mobile element).
The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus.
No sample metadata fields
View SamplesPin1 inhibiton exerts anti-oncogenic effects on LNCaP and DU145 cells despite the gene regulation patterns by Pin1 were different in both cells.
Pin1 Inhibitor Juglone Exerts Anti-Oncogenic Effects on LNCaP and DU145 Cells despite the Patterns of Gene Regulation by Pin1 Differing between These Cell Lines.
Specimen part, Cell line
View Samples