Aging is a key factor in Alzheimer''s disease, but it''s correlation with the pathology and pathological factors like amyloid-beta remains unclear In our study we aimed to provide an extensive characterisation of age-related changes in the gene expression profile of APP23 mice and controls and correlate these changes to pathological and symptomatic features of the model We found a clear biphasic expression profile with a developmental and aging phase. The second phase, particularly, displays aging features and similarties with the progression of Alzheimer pathology in human patients Processes involved in microglial activation, lysosomal processing, neuronal differantion and cytoskeletal regulation appear key factors in this stage. Interestingly, the changes in the gene expression profile of APP23 mice also seem to occur in control animals, but at a later age. The changes appear accelerated and/or exacerbated in APP23 mice. Overall design: mRNA profiles of APP23 mice and wild-type control littermates aged 1.5, 6, 18 or 24 months. For all the age groups, samples of 3 mice of each genotype were analyzed
Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease.
Age, Specimen part, Subject
View SamplesBackground: Tissue macrophages contribute to development and protection, both requiring appropriately timed and located source(s) of factors controlling growth, cell differentiation and migration. Goal: To understand the role of microglia (tissue macrophages of the central nervous system), in promoting neurodevelopment and controlling neuroinflammation. Summary of findings: We show that microglia fulfill both these roles. In contrast to adult cells, neonatal microglia show a unique neurogenic phenotype with stem cell-like potential. Neonatal microglia are protective against neuroinflammation, and their transplantation ameliorates experimental autoimmune encephalomyelitis. A CD11c+ microglial subset predominates in primary myelinating areas of the developing brain and expresses genes for neuronal and glial survival, migration and differentiation. CD11c+ microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neurogenic neonatal microglia characteristics. Conclusions: We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for neurogenesis and myelination and suppress neuroinflammation. Overall design: The overall design was to compare transcriptomes of subsets of microglia isolated from neonatal mice, healthy adults, and adult mice with a neuroinflammatory disease (Experimental autoimmune encephalomyelitis, EAE), and to compare anti-inflammatory function of adult and neonatal microglia. Microglia were isolated by cell-sorting based on surface phenotype, and RNAseq data was analyzed using WGCNA, GO and DAVID approaches. Expression of selected genes and pathways was confirmed by histology and flow cytometry. Functional analysis involved transfer of isolated microglia to the central nervous system of animals with EAE and evaluation of outcome. EAE = Experimental autoimmune encephalomyelitis
A novel microglial subset plays a key role in myelinogenesis in developing brain.
Subject
View SamplesAlthough the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades, the survival chances for infants (<1 year of age) with ALL remains poor.
Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia.
Sex, Specimen part, Disease
View SamplesTumor epithelium and surrounding stromal cells were isolated using laser capture microdissection of human breast cancer to examine differences in gene expression based on tissue types from inflammatory and non-inflammatory breast cancer
A stromal gene signature associated with inflammatory breast cancer.
Specimen part, Disease, Race, Subject
View SamplesTo examine Ikaros tumor suppressor mechanisms, we have utilized inducible RNAi to dynamically restore endogenous Ikaros expression in BCR-ABL1+ B-ALL driven by its knockdown (Ikaros knockdown), and compared these tumors to tumors driven by BCR-ABL1 alone (control). Restoration of Ikaros causes rapid regression of tumor cells in vivo, significantly prolonging tumor transplant recipient survival. Using both transgenic and retroviral approaches, we conducted expression analysis of B-ALL by RNA-Seq and have identified a series of Ikaros-regulated genes within established tumor cell in vivo. Comparison of Ikaros-activated and Ikaros-repressed genes with human B-ALL expression data shows a set of conserved Ikaros target genes, some of which are associated with patient outcome (namely, CTNND1, IFITM3 and EMP1). Overall design: RNA-seq was performed on BCR-ABL1+ B-ALL with inducible Ikaros knockdown (Ikaros knockdown, n=8; transgenic n=5, retroviral n=3) or BCR-ABL1+ alone B-ALL (control, n=4; transgenic n=3, retroviral n=1) cells isolated from untreated and three 3-day Dox-treated mice. Samples were run on HiSeq or NextSeq platform. B-ALL B031 was run in technical duplicate. Extended Dox samples (B027: d7 and d10) and relapse samples for B027, B029 and B035 have also been analyzed in this dataset.
Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome.
Specimen part, Treatment, Subject
View SamplesPlants are known to be responsive to volatiles, but knowledge about the molecular players involved in transducing their perception remain scarce.
WRKY40 and WRKY6 act downstream of the green leaf volatile E-2-hexenal in Arabidopsis.
Treatment
View SamplesHeterologous expression of the fungal pathogen Cladosporium fulvum Avr2 in Arabidopsis plants.
The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense.
No sample metadata fields
View SamplesTitle: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA.
Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.
No sample metadata fields
View SamplesFrozen tissue specimens from primary breast tumors were collected and profiled using Affymetrix U133 plus 2 expression microarrays.
Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells.
Specimen part, Disease, Disease stage
View SamplesMania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individual without a psychiatric disorder. We found that a history of eating nitrated dry cured meat, but not other meat or fish products, was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p<8.97x 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in alterations in behavior and changes in intestinal microbiota. Rats fed diets with added nitrate also showed alterations of brain pathways dysregulated in mania. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions
Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats.
Sex, Specimen part
View Samples