Microglia play important roles in developmental and homeostatic brain function, and influence the establishment and progression of many neurological disorders. Here, we demonstrate that renewable human iPSCs can be efficiently differentiated to microglial-like cells (iMGL) to study neurological diseases, such as Alzheimer''s disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to adult and fetal human microglia. Functional assessment of iMGLs reveal that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. We also show novel use of iMGLs to examine the effects of fibrillar Aß and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Taken together, these findings demonstrate that iMGLs can be used in high-throughput studies of microglial function, providing important new insight into human neurological disease. Overall design: Human cells were collected and analyzed for gene expression using RNA-seq.
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
Specimen part, Subject
View SamplesWe used transverse aortic constraction pressure overload hypertrophy mouse hearts as a model of cardiovascular disease to study the genetic changes between TAC and SHAM (normal) mouse hearts and over 1 circadian cycle (24h). This is one approach to identify diurnal genetic biomarkers of cardiovascular disease.
Chronomics of pressure overload-induced cardiac hypertrophy in mice reveals altered day/night gene expression and biomarkers of heart disease.
Specimen part, Disease, Disease stage, Time
View SamplesCritical disease caused by the new 2009 pandemic influenza virus (nvH1N1) is a challenge for physicians and scientist. As evidenced in SARS and H5N1, the development of an effective immune response plays a key role to overcome viral diseases. We studied host`s gene expression signatures, cytokine and antibody responses along the first week of hospitalization in 19 critically ill patients with primary nvH1N1 pneumonia and two degrees of respiratory involvement. Presence of comorbidities and absence of immunosuppresory conditions were the common antecedents in both groups. The most severe patients (n=12) showed persistant respiratory viral secretion, increased levels of pro-inflammatory cytokines and chemokines in serum, and elevated systemic levels of two immunosuppresory cytokines (IL-10 and IL-1ra). Both groups were able to produce specific antibodies against the virus. The average day for antibody production was day 9 in the course of the disease, defining an early period of innate immunity and a late period of adaptive immunity. The most severe group evidenced a poor expression of a set of MHC class II and T cell receptor (TCR) related genes participating in antigen presentation and cell mediated immune responses in the late phase. 7 patients of this group finally died. This findings evidence that, as observed in sepsis, severe H1N1 disease course with immunoparalysis, which could explain the poor control of the virus along with the increased incidence of bacterial superinfection observed in these patients.
Host adaptive immunity deficiency in severe pandemic influenza.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Specimen part
View SamplesWe demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in hiPSC-derived neural progenitor cells (hiPSC-NPC) is sufficient to rapidly generate O4+ oligodendrocytes with an efficiency of 60 to 70% within 28 days.
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Specimen part
View SamplesAllergic diseases correspond to a broad range of hypersensitivity reactions, often occurring as co-morbidities. Investigation of the molecular basis of allergy is a challenge because of its highly heterogeneous nature. We combined large-scale and high-throughput gene expression technology and systems biology approaches to retrieve relevant biomarkers and signalling pathways.
A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents.
Sex, Age, Specimen part
View SamplesAllergic diseases correspond to a broad range of hypersensitivity reactions, often occurring as co-morbidities. Investigation of the molecular basis of allergy is a challenge because of its highly heterogeneous nature. We combined large-scale and high-throughput gene expression technology and systems biology approaches to retrieve relevant biomarkers and signalling pathways.
A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents.
Sex, Age, Specimen part
View SamplesBackground: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells.
Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa.
Specimen part
View SamplesMesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibers through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
Sex, Specimen part
View SamplesTo study the effect of miR-130a in prostate cancer, PC3 cells overexpressing miR-130a were analyzed for global gene expression.
Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1.
Cell line
View Samples