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SRP119053
Homo sapiens
278 Downloadable Samples
Illumina HiSeq 2500
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: We profiled the human HSCe (Lineage-, CD34+, CD38-) transcriptome with aging at the single cell level. Single-cell RNAseq was performed on FACS isolated human bone marrow derived HSCe from 5 young (24-37 yo) and 4 aged donor (64-71 yo). Donors had no known hematological malignancy.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: CRISPR-Cas9 mediated knockout of KLF6 was performed in human peripheral blood CD34+ cells (n=4 replicates). RNA-seq was utilized to determine the effect of KLF6 knockout compared to a non-targeting control control.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To improve our understanding of the relationships between methylation and expression we profiled mRNA expression and single-base resolution methylation levels for two breast cancer cell lines, MCF7 and T47D. Expression was profiled using RNA-seq. Methylation was assayed using Methyl-MAPS, which uses methylation-sensitive and -dependent restriction enzyme digests followed by high-throughput sequencing to identify methylation levels at individual CpGs (Edwards et al. 2010, Genome Research). Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7 and T47D cells under standard growth conditions.
Publication Title
Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Approximately 75% of breast cancers express estrogen receptor a (ERa) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit estrogen receptor signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the up-regulation of alternative growth signals. The mechanisms that drive this resistance - especially epigenetic events that alter gene expression - are however not well understood. Here we performed a genome-wide DNA methylation and expression analysis of cell line models to find epigenetically regulated genes involved in acquired aromatase inhibitor resistance. We discovered that prostaglandin E2 receptor 4 (PTGER4) is up-regulated after demethylation and promotes phosphorylation and activation of ERa. Knockdown and inhibitor studies demonstrate that PTGER4 promotes AI resistance via ligand independent activation of the ERa-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate that PTGER4 is a potential drug target in AI resistant cancers. Additionally, the epigenetic component of PTGER4 regulation suggests that further study of PTGER4 may yield valuable insights into how DNA methylation-targeted diagnoses and/or treatments can improve AI resistant breast cancer treatment. Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7-LTED (long-term estrogen deprived) cells grown in charcoal stripped serum. Two replicates were performed.
Publication Title
Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
Publication Title
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. We have investigated the molecular mechanisms responsive to in-house fabricated citrate coated SPIONs (C-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. C-SPIONs (500 g/ml) affected the transcriptional response of signal transduction cascades (i.e. TFG-beta), protein processing in the endoplasmic reticulum, and RNA transport, among other biological processes. They also triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Interestingly, other pathways frequently linked to nanotoxicity like oxidative stress or apoptosis were not identified as significantly affected in this genome-wide in vivo study despite the high dose of exposure.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. Different NP coatings are being explored, among them albumin which has been applied in some drugs delivery systems. We have investigated the molecular mechanisms responsive to in-house fabricated SPIONs coated with bovine serum albumin (BSA-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. BSA-SPIONs (500 g/ml) affected the transcriptional response of glycan metabolic pathways related to innate immune response, xenobiotics degradation, and triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Remarkably, key biological functions such as apoptosis or protein processing were not affected with significance despite the high dose of exposure.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples