Periostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity. By differential gene expression we evaluated putative targets involved in those cellular properties.
Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.
Specimen part, Cell line
View SamplesTime-point expression analysis of fractures calluses at 1, 3, and 5 days post-fracture in young and old BALB/c mice.
Identification of novel gene expression in healing fracture callus tissue by DNA microarray.
Age, Specimen part
View SamplesTGF ligands act as tumor suppressors in early stage tumors but are paradoxically diverted into potent prometastatic factors in advanced cancers. The molecular nature of this switch remains enigmatic. We now show that TGF-dependent cell migration, invasion and metastasis are empowered by mutant-p53.
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.
No sample metadata fields
View SamplesMyelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. Overall design: mRNA profiling in bone marrow mononuclear cells (BM MNC) from 14 CMML patients (8 decitabine responders vs. 6 non-responders).
Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.
No sample metadata fields
View SamplesThe goals of this study are to compare transcriptome profiling (RNA-seq) of patients BM with or without ASXL2 mutations. Overall design: Patient bone marrow mRNA profiles with or without ASXL1/2 mutations were generated by deep sequencing
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
Specimen part, Subject
View SamplesThe goals of this study are to compare transcriptome profiling (RNA-seq) of Asxl2 KO LSK cells to that of Asxl2 wild-type cells. We found substantial number of genes are differentially expressed in Asxl2 KO cells. Overall design: LSK mRNA profiles of Asxl2-/- mice and Asxl2wt/wt (WT) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
Specimen part, Cell line, Subject, Compound
View SamplesWe previously showed that severe liver diseases are characterized by expansion of liver progenitor cells (LPC), which correlates with disease severity. However, the origin and role of LPC in liver physiology and in the hepatic response to injury remains a contentious topic. We have now used genetic lineage tracing of Hnf1-expressing biliary duct cells to assess their contribution to LPC expansion and hepatocyte generation during normal liver homeostasis, and following different types of liver injury. We found that ductular reaction cells in human cirrhotic livers express HNF1. However, HNF1 expression was not present in newly generated EpCAM-positive hepatocytes. Using a tamoxifen-inducible Hnf1CreER/R26RYFP/LacZ mouse, we show that there is no contribution of the biliary epithelium to hepatocyte turnover during liver homeostasis in healthy mice. Moreover, after loss of liver mass, Hnf1+ LPC did not contribute to hepatocyte regeneration. We also assessed the contribution of Hnf1+ cells following acute and repeated liver injury. All animal models showed expansion of LPC, as assessed by immunostaining and gene expression profile of sorted YFP-positive cells. A contribution of Hnf1+ LPC to hepatocyte generation was not detected in animal models of liver injury with preserved hepatocyte regenerative potential such as acute acetaminophen, carbon tetrachloride injury, or chronic diethoxycarbonyl-1,4-dihydro-collidin (DDC)-diet. However, in mice fed with choline-deficient ethionine-supplemented (CDE)-diet, which causes profound hepatocyte damage and arrest, a small number of hepatocytes were derived from Hnf1+ cells. Conclusion: Hnf1+ cells do not participate in hepatocyte turnover in the healthy liver or during liver regeneration after partial hepatectomy. After liver injury, LPC arise from the biliary duct epithelium, which gives rise to a limited number of hepatocytes only when hepatocyte regeneration is compromised.
The biliary epithelium gives rise to liver progenitor cells.
No sample metadata fields
View SamplesCD34 positive cells of bone marrow samples from normal and MDS samples were cultured ex vivo into erythroid conditions.
Defective nuclear localization of Hsp70 is associated with dyserythropoiesis and GATA-1 cleavage in myelodysplastic syndromes.
Specimen part
View SamplesAnalysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA.
Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.
Specimen part, Disease, Disease stage
View SamplesWe analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.
Specimen part, Cell line
View Samples