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SRP195539
Homo sapiens
22 Downloadable Samples
Illumina HiSeq 4000, NextSeq 500
Description
It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271+ NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271+ cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271+ NSCs to the SVZ homogenate from control donors to assess the CD271+ NSCs gene signature and finally made a comparison between controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also suggest that NSCs may transit into a primed-quiescent state, that is in an “alert” non-proliferative phase in PD. Overall design: From post-mortem human SVZ of control and Parkinson disease donors we isolated CD271+ NSCs and Cd11b+ microglia by MACS and the whole SVZ to generate RNA sequencing libraries using Celseq2 method. We aimed for low coverage sequencing (~2 million mapped to the coding regions) per sample to investigate the gross changes in the transcriptome. Libraries (rpi small primer) were sequenced in 3 runs, 2 on an Illumina NextSeq500 using 75-bp paired-end sequencing at the Utrecht Seuqencing center (USEQ) and the third on a HiSeq4000 using 150-bp paired-end sequencing at Genomescan. All the samples were mapped in a single run to an average depth of ~10 million reads per sample. Reads were mapped to the latest human coding transcriptome using bwa, normalized and analyzed using the standard DESEQ2 package.
Publication Title
Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development.
Publication Title
A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Embryonic CNS neurons can differentiate in culture and provide a model for maturation-related changes. A transcriptome profile over the course of maturation was perform to investigate the underlying molecular mechanism that drives maturation and its related changes such as developmental loss of intrinsic regenerative capacity. Overall design: Primary cortical neurons were excised from E18 rat embryos and were co-cultured with primary rat astrocytes from P0-2 rats. RNA were then extracted on day 1, 4, 8, 16, and 24 after plating.
Publication Title
Selective rab11 transport and the intrinsic regenerative ability of CNS axons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 340 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
In our early study (PMID: 21939527), we have created a ClinicoMolecular Triad Classification (CMTC) to improve prediction and prognostication of breast cancer by using a training cohort contained 161 breast cancer patients (2003 to 2008). Here, a supplemental internal validation cohort contained 340 breast cancer patients was collected (2008 to 2010) for development of the CMTC.
Publication Title
Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.
Sample Metadata Fields
Age, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Assessment of p53 targets by gene expression array analysis in irradiated and nonirradiated Wip1+/+ and Wip1-/- MEFs.
Publication Title
The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis. Overall design: Human CD14+ MCSF-differentiated macrophages were cultured with or without synovial fibroblasts in transwell chambers. TNF was added at Day 0, macrophages were harvested at Day 2. Total of 4 samples: (1) macrophages alone (2) macrophages with fibroblasts (3) macrophages with TNF (4) macrophages with fibroblasts and TNF. Macrophage RNA was purified using RNeasy mini kit (Qiagen). Tru-seq sample preparation kits (Illumina) were used to purify poly-A transcripts and generate libraries with multiplexed barcode adaptors. All samples passed quality control on a Bioanalyzer 2100 (Agilent). Paired-end reads (50 x 2 cycles, ~75x106 reads per sample) were obtained on an Illumina HiSeq 2500. The TopHat program was used to align the reads to the UCSC Hg19 human reference genome, while the Cufflinks program allowed for measurements of transcript abundance (represented by Fragments Per Kilobase of exon model per Million mapped reads (FPKM)).
Publication Title
Modulation of TNF-induced macrophage polarization by synovial fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 161 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
When making treatment decisions, oncologists often stratify breast cancers into a low-risk group (ER+, low grade); an intermediate-risk group (ER+, high grade); and a high-risk group that includes Her2+ and triple-negative (ER-/PR-/Her2-) tumors. None of the currently available gene signatures correlates to this clinical classification. We aimed to develop a test that is practical for the oncologists, that offers both molecular characterization of BCs, and improved prediction of prognosis and treatment response. We investigated the molecular basis of such clinical practice by grouping Her2+ and triple-negative breast cancers together during clustering analyses on the genome-wide gene expression profiles of our training cohort, mostly derived from fine needle aspiration biopsies (FNABs) of 149 consecutive evaluable Breast cancers. The analyses consistently divided these tumors into a three-cluster pattern, similar to clinical risk-stratification groups, that was reproducible in published microarray databases (n=2487) annotated with clinical outcomes. The clinicopathologic parameters of each of these three molecular groups were also similar to clinical classification. The low-risk group had good outcomes and benefited from endocrine therapy. Both intermediate- and high-risk groups had poor outcomes and were resistant to endocrine therapy. The latter demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in MYC, E2F1, Ras, -Catenin and IFN- pathways; and poor prognosis predicted by 14 independent prognostic signatures. Based on a multivariate analysis, this new gene signature, termed ClinicoMolecular Triad Classification, predicted recurrence and treatment response better than all pathologic parameters and other prognostic signatures.
Publication Title
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
To measures the comparability and concordance of Illumina microarray, a series of 30 samples of Universal Human Reference RNA (UHRR) were set as controls for every single chip of total 30 Human-Ref V2 BeadChips. The average bead number of the 30 arrays was 42.38.1 for any bead type over the 22,184 probes. A high average correlation coefficient (r) value was obtained as 0.99080077 relative to each other of the expression intensity values from the 30 duplicate UHRR samples.
Publication Title
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Age-related defects in stem cells can limit proper tissue maintenance and hence contribute to a shortened life-span. Using highly purified hematopoietic stem cells from mice aged 2 to 21 months, we demonstrate a deficit in function yet an increase in stem cell number with advancing age. Expression analysis of more than 14,000 genes identified 1500 that were age-induced and 1600 that were age-repressed. Genes associated with the stress response, inflammation, and protein aggregation dominated the upregulated expression profile, while the downregulated profile was marked by genes involved in the preservation of genomic integrity and chromatin remodeling. Many chromosomal regions showed coordinate loss of transcriptional regulation, and an overall increase in transcriptional activity with aged, and inappropriate expression genes normally regulated by epigenetic mechanisms was observed. Hematopoietic stem cells from early-aging mice expressing a mutant p53 allele reveal that aging of stem cells can be uncoupled from aging at an organismal level. These studies show that HSC are not protected from aging. Instead, loss of epigenetic regulation at the chromatin level may drive both functional attenuation of cells, as well as other manifestations of aging, including the increased propensity for neoplastic transformation.
Publication Title
Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
KLF5 is a basic transcription factor that regulates multiple biological processes, but its function in tumorigenesis appears contradictory in the current literature, with some studies showing tumor suppressor activity and others showing tumor promoting activity. In this study, we examined the function of Klf5 in prostatic tumorigenesis using mice with prostate specific deletion of Klf5 and Pten, both of which are frequently deleted in human prostate cancer. Histological and molecular analyses demonstrated that when one Pten allele was deleted, which causes mouse intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth and caused more severe morphological and molecular alterations, and homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Klf5 deletion clearly promoted tumorigenesis in luminal cells, it actually diminished the numbers of Ck5-positive basal cells in the Pten-null tumors. Klf5 deletion also increased the cell proliferation rate in tumors with Pten deletion, which involved extensive activation of the PI3K/AKT and MAPK mitogenic signaling pathways and inactivation of the p15 cell cycle inhibitor. Global gene expression and pathway analyses demonstrated that multiple mechanisms could be responsible for the tumor promoting effect of Klf5 deletion,
Publication Title
Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples