Recently, the bone marrow (BM) has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of nave and an increase in effector-memory T cells. In contrast to the peripheral blood (PB), a highly activated CD8+CD28 T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation and differentiation of CD8+ T cell in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28 T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28 T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
The impact of aging on memory T cell phenotype and function in the human bone marrow.
Sex, Age
View SamplesThe cell of origin for rhabdomyosarcoma (RMS) and undifferentiated pleomorphic sarcoma (UPS) remains to be determined. We utilized two skeletal muscle specific inducible Cre mouse lines to transform both skeletal muscle stem cells and progenitors to determine which cells give rise to RMS and UPS.
Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.
No sample metadata fields
View SamplesWe isolated and selected intestinal adenoma organoids from Apcmin/+; Rosa26LSL-TdTomato; Prox1-CreERT2 mice. After the selection procedure without growth factors, we induced CreERT2 activity and the transcription of tdTomato to label Prox1+ cells by 300 nM 4-hydroxytamoxifen for 16h. tdTomato+ (Prox1+) and tdTomato- cells (enriched for Prox1- cells) were FACS sorted and total RNA was isolated.
Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells.
Specimen part
View SamplesHuman lung cancer (A549) cells were treated 50uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd) for 4, 12, and 24 hrs and expression compared to control cells (treated with 5% mannitol for the same length of time)
Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.
No sample metadata fields
View SamplesPaired samples from human femoral artery lesions were obtained during intravascular surgery exploiting Silverhawk device
Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster.
Sex, Age, Specimen part
View SamplesPurpose: The goal of this study was to assess gene expression changes in neurons overexpressing SOX5 using human primary neuronal culture system. Methods: 6 samples each from control GFP and SOX5 overexpressing neurons were used to isolate total RNA using miRNeasy kit, Qiagen. We performed rRNA-depleted 69bp paired end stranded RNA-seq on neurons overexpressing either GFP or SOX5 tagged with GFP. Overexpression of SOX5 in neurons validated that a significant proportion of Attenuated cortical patterning (ACP) genes are regulated by SOX5, and that predicted SOX5 targets exhibit a net downregulation, consist with its repressive function. This supports the prediction that attenuated patterning of SOX5 between cortical regions contributes to direct alterations in SOX5 targets and likely to indirect alterations in SOX5 non-targets in the ACP set. delpleted 69 bp stranded RNA-seq in Overall design: SOX5 was overexpressed in primary human neuronal cultures using a lentiviral system. Briefly full-length human SOX5 gene was cloned in pLVU/GFP vector (gift from Lars Ittner [Addgene plasmid #24177]) using the gateway recombination technique. Lentivirus was produced in HEK293T cells using a second generation packaging vector system (psPAX2, a gift from Didier Trono [Addgene plasmid #12260] and pCMV-VSV-G, a gift from Bob Weinberg [Addgene plasmid #8454]) as described by Stewart et al., 200331. Primary human neurons were infected at plating at a multiplicity of infection (MOI) of 10 with either the SOX5 overexpressing construct or a control pLVU-GFP backbone vector. 14 days after infection, RNA from the samples were isolated using miRNeasy micro kit (Qiagen, Carlsbad) and 50bp paired-end libraries were prepared using SMARter Stranded Total RNA sample prep kit (Clontech) with rRNA depletion. Libraries were then multiplexed and sequenced with HiSeq 2500 instrument (Illumina).
Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism.
Specimen part, Treatment, Subject
View SamplesTo uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors.
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.
Sex, Specimen part
View SamplesAlternative splicing of pre-mRNA generates protein diversity and has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantication of expression levels for the majority of exons and facilitates the discovery of alternative splicing events. Analysis of exon array data is more challenging than gene expression data and there is a need for reliable quantication of exons and alternative spliced variants. We introduce a novel, computationally efficient methodology, MEAP, for exon array data preprocessing, analysis and visualization. We compared MEAP with other preprocessing methods, and validation of the results show that MEAP produces reliable quantication of exons and alternative spliced variants. Analysis of data from head and neck squamous cell carcinoma (HNSCC) cell lines revealed several variants associated with 11q13 amplication, which is a predictive marker of metastasis and decreased survival in HNSCC patients. Together these results demonstrate the utility of MEAP in suggesting novel experimentally testable predictions. Thus, in addition to novel methodology to process large-scale exon array data sets, our results provide several HNSCC candidate genes for further studies.
Comprehensive exon array data processing method for quantitative analysis of alternative spliced variants.
Cell line
View SamplesWild type Columbia and serrate-1 globular stage embryos were sequenced in order to profile miRNAs which are expressed in embryogenesis in Arabidopsis thaliana Overall design: Two biological replicates, two conditions
Arabidopsis thaliana miRNAs promote embryo pattern formation beginning in the zygote.
Specimen part, Subject
View SamplesTo study the role of epigenetics and hormones on hematopoietic stem cell function, hematopoietic stem and progenitor (LSK) cells were sorted from E14.5 embryos of wild-type, DNMT3B7 hemizygous or DNMT3B7 homozygous genotype. The expression analysis was performed to provide information regarding the mechanism by which hormones regulate hematopoiesis. Overall design: Hematopoietic stem and progenitor (LSK) cells from E14.5 murine embryonic fetal livers of wild-type, or DNMT3B7 transgenic genotypes were flow-sorted, and RNA isolated for expression analysis by RNA-Sequencing
Epigenetic Control of Apolipoprotein E Expression Mediates Gender-Specific Hematopoietic Regulation.
No sample metadata fields
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