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Homo sapiens
138 Downloadable Samples
Description
Multiple myeloma (MM) is a malignant plasma cell disorder with well-defined clonal genetic/cytogenetic abnormalities. However, cellular heterogeneity is a key factor in MM's progression, therapeutic decision, and response to treatment. Single cell whole transcriptome profiling (scRNA-Seq) offers an opportunity to dissect this molecular heterogeneity during MM progression to better understand the disease and guide rational therapy. Here, we examined 597 CD138 positive cells from 15 patients at different stages of MM progression using scRNA-Seq. We selected 790 genes based on a Coefficient of Variation (CV) approach which organized cells into four clusters (L1-L4) based on unsupervised clustering. Plasma cells from each patient contained a mixed population of plasma cells at different state of aggressiveness based on gene expression signature reflecting the inter-cellular heterogeneous nature of MM. Cells in the L1 group is characterized by low level expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathway having most cells from MGUS patients (p < 1.2x10-14). In contrast, low level of these genes in L1 group increased progressively and were the highest in the L4 group containing only cells from high-risk MM patients with t(4;14) translocations. Furthermore, 44 genes consistently overexpressed by pair-wised comparisons of the four groups strongly associated with a reduced overall survival in MM patients (APEX trial, p < 0.0001; Hazard Ratio (HR), 1.83; 95% CI, 1.33 to 2.52), particularly those in the bortezomib treated group (p < 0.0001; HR, 2.00; 95% CI, 1.39 to 2.89). No survival significance was observed for the dexamethasone treated group. Our study at the resolution of single cells showed that there is a mixed population of cells in each patient at different stages of MM progression and these cells can be organized into four different subgroups (L1 to L4). Consistent overexpression of the 44 genes from L1 to L4 groups is associated with patient outcome and treatment response. Our results show that oxidative phosphorylation, Myc target, and mTORC1 signaling genes are significant pathways for MM progression and affect MM prognosis and treatment stratification. Overall design: 597 single cell libraries passed QC and were included in the downstream analysis
Publication Title
Molecular signatures of multiple myeloma progression through single cell RNA-Seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 161 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH3 transcriptional module induces cell motility in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Migratory embryonal neuroblasts give rise to several tissues, including the sympathetic nervous system (SNS). Neuroblastomas are paediatric tumours of the peripheral SNS with a highly variable prognosis. We observed that high NOTCH3 expression in neuroblastomas correlated with a poor prognosis. Expression of a NOTCH3 transgene in neuroblastoma cells induced many motility genes and conferred a highly motile phenotype. Expression of these motility genes strongly correlated with NOTCH3 expression in neuroblastomas and many other tumours, suggesting a general role for NOTCH3 in regulation of these genes. Silencing of NOTCH3 or genes of the Notch-processing -secretase complex induced apoptosis in all neuroblastoma cell lines tested. These data suggest that NOTCH3 is a key-regulator of motility, and indispensable for survival of neuroblastoma cells.
Publication Title
A NOTCH3 transcriptional module induces cell motility in neuroblastoma.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 44 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide analysis of gene expression in response to bortezomib treatment (33 nM) in cell lines before and after selection for resistance.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide analysis of gene expression in response to bortezomib treatment(33 nM) in cell lines before and after selection for resistance.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization.
Publication Title
Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 543 Downloadable Samples
- Illumina HiSeq 2000
Description
Single cell sequencing of microglia and perivascular macrophages was performed on brain tissue from different brain regions to obtain single cell expression profiles dependent on celltype and regional location. Overall design: 425 cells from mouse (CD-1) brains at different postnatal ages as well as embryonic day E11.5-E18.5.
Publication Title
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 3000
Description
Microglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses, which were transcriptionally different from perivascular macrophages, in up to six different CNS regions during development and diseases. Single-cell analysis revealed specific time- and region-dependent microglia subtypes during homeostasis. In contrast, demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Finally, diverse microglia subsets were also identified in normal and diseased human brains. Our data provide new insights into the CNS endogenous immune system during development, health and perturbations. Overall design: CD45+ cells isolated from healthy and MS-affected human brains were FACS-sorted in 384-well plates and used for scRNAseq. The patients were aged between 22 and 25 years. Data comprises 5 healthy and 5 MS patients. CEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016).
Publication Title
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE144829- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Different osteoprogenitors (SSC, BCSP, Thy+) were sorted after 2 days of JUN induction, followed by RNA extraction and microarray analysis
Publication Title
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures.
Sample Metadata Fields
Specimen part
View Samples