This is a study to explore the transcriptional changes after Adjudin treatment in adult rat testes at three time points (control, 8 hour and 4 day). Adjudin, [1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide], is a potential male contraceptive that targets the Sertoli-germ cell interface and causes germ cell depletion from the seminiferous epithelium. Adjudin has been proved to be a useful model to study the mechanisms that regulate junction restructuring in the testis.
Unraveling the molecular targets pertinent to junction restructuring events during spermatogenesis using the Adjudin-induced germ cell depletion model.
No sample metadata fields
View SamplesOur hypothesis was that at any given point in time, islets will contain differing populations of beta cells at different stages of their lifecycle, with further changes occurring with metabolic stress and aging. We examined subpopulations of beta cells isolated from MIP-GFP mice on the basis of their insulin transcriptional activity and in their expression of p16Ink4a. In addition, using aging C57Bl/6 mice as a model, markers of beta cell aging were identified and validated: Igf1r and Cd99 expression increased with age, whereas Kcnq5 was decreased with age. These markers were correlated with an age-related decline in function. The functional aging of beta cells was accelerated by S961, an antagonist to the insulin receptor, which induced insulin resistance. Particularly surprising was the finding of marked islet heterogeneity as demonstrated with the marked staining differences of the markers: Igf1r, Cd99 and Kcnq5. These novel findings about beta cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions that must be addressed about the pathogenesis of type 2 diabetes. The present study has identified new markers of aging in beta cells and found that the expression of these and other markers can be increased by insulin resistance. This provides insight into how insulin resistance might accelerate the death of beta cells. In addition, striking heterogeneity among islets was found, which opens up new ways to think about islet biology and the pathogenesis of T2D.
β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance.
Age, Specimen part
View SamplesThe goal of this study was to determine developmental differences in gene expression between left and right ventricle, and to assess the differential effect of altered hemodynamic loading on left and right ventricle. Chick ventricles from different developmental stages were isolated for assessment of normal developmental profiles. Conotruncal banding or partial ligation of the left atrial appendage was performed in ovo at embryonic day 4 and ventricles were isolated at embryonic day 5 (banding) or 8 (ligation) for assessment of altered loading effects.
Microarray analysis of normal and abnormal chick ventricular myocardial development.
Specimen part
View SamplesHuman mesenchymal stem cells (MSC) display a high potential for the development of novel treatment strategies for cartilage repair. However, the pathways involved in their differentiation to functional and non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including members of the TGF, Hh, Wnt and FGF families. In this study, we asked if we could identify specific biological networks independently from the growth factor used (TGF-3 or BMP-2). To address this question, we used DNA microarrays and performed large-scale expression profiling of MSC at different time points during their chondral differentiation. By comparing these data with those obtained during their differentiation into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis. We distributed the selected genes in 5 classes according to their kinetic of expression and used the Ingenuity software in order to identify new biological networks. We could reconstruct 3 phases for chondral differentiation, characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis prevention with the up-regulation of 5 integrins, BCL6, NFIL3, RGS2 and down-regulation of CTGF and CYR61. The second phase is characterized by a proliferation/differentiation step with the continuous expression of MAF, PGF, HGMA1 or NOTCH3, CHI3L1, WNT5A, LEPR. Finally, the last step of differentiation/hypertrophy is characterized by expression of DKK1, APOD/E, SERPINF1 and TIMP4. These data propose new pathways to understand the complexity of MSC differentiation to chondrocytes and new potential targets for cell therapy applied to cartilage repair.
Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis.
No sample metadata fields
View SamplesWe show that resident macrophages accumulate in cilia mutant mice prior to cyst formation and that inhibition of resident macrophage accumulation reduces cystic kidney disease. Overall design: We analyzed gene expression of R2a (CD11c+) and R2b (CD11c-) resident macrophages isolated from adult, wild type mice. In these experiments, we isolated RNA from 6-8 mice and pooled the RNA together prior to sequencing.
Tissue-Resident Macrophages Promote Renal Cystic Disease.
Age, Specimen part, Cell line, Subject
View Samples