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Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2000
Description
Down syndrome (DS), a complex genetic disorder caused by chromosome 21 trisomy, is associated with mitochondrial dysfunction leading to the accumulation of damaged mitochondria. Here we report that mitophagy, a form of selective autophagy activated to clear damaged mitochondria is deficient in primary human fibroblasts derived from individuals with DS leading to accumulation of damaged mitochondria with consequent increases in oxidative stress. We identified two molecular bases for this mitophagy deficiency: PINK1/PARKIN impairment and abnormal suppression of macroautophagy. First, strongly downregulated PARKIN and the mitophagic adaptor protein SQSTM1/p62 delays PINK1 activation to impair mitophagy induction after mitochondrial depolarization by CCCP or antimycin A plus oligomycin. Secondly, mTOR is strongly hyper-activated, which globally suppresses macroautophagy induction and the transcriptional expression of proteins critical for autophagosome formation such as ATG7, ATG3 and FOXO1. Notably, inhibition of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) using AZD8055 (AZD) restores autophagy flux, PARKIN/PINK initiation of mitophagy, and the clearance of damaged mitochondria by mitophagy. These results recommend mTORC1-mTORC2 inhibition as a promising candidate therapeutic strategy for Down Syndrome. Overall design: mRNA-Seq profiling of 9 2N and 8 DS human fibroblasts samples of age 5 months (< 1 year) and 2 years. These samples come from 5 unrelated 2N individuals (of which 2 individuals, one each of 5 months and 2 years, have 3 replicates each) and 3 unrelated DS individuals (of which 2 individuals, one each of 5 months and 2 years, have 3 replicates each). Five samples were reanalyzed from GSE55504.
Publication Title
mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Thirty to 60% of CD56dimCD16bright NK cells in healthy adults express CD57, which is not expressed on immature CD56bright NK cells or fetal and newborn NK cells. We hypothesized that CD57+ NK cells within the CD56dim mature NK cell subset are highly mature and might be terminally differentiated.
Publication Title
CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset.
Sample Metadata Fields
Specimen part, Subject
View Samples- Zea mays
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
Endosperm is an absorptive structure that supports embryo development or seedling germination in angiosperms. The endosperm of cereals is a main source of food, feed, and industrial raw materials worldwide. However, the gene regulatory networks that control endosperm cell differentiation remain largely unclear. As a first step toward characterizing these networks, we profiled the mRNAs in five major cell types of the differentiating endosperm and in the embryo and four maternal compartments of the kernel. Comparisons of these mRNA populations revealed the diverged gene expression programs between filial and maternal compartments, and an unexpected close correlation between embryo and the aleurone layer of endosperm. Gene co-expression network analysis identified co-expression modules associated with single or multiple kernel compartments including modules for the endosperm cell types, some of which showed enrichment of previously identified temporally activated and/or imprinted genes. Detailed analyses of a co-expression module highly correlated with the basal endosperm transfer layer (BETL) identified a regulatory module activated by MRP-1, a regulator of BETL differentiation and function. These results provide a high-resolution atlas of gene activity in the compartments of the maize kernel and help to uncover the regulatory modules associated with the differentiation of the major endosperm cell types. Overall design: RNAs from ten compartments of the maize kernel including the central starchy endosperm (CSE), conducting zone (CZ), aleurone (AL), basal endosperm transfer layer (BETL), embryo-surrounding region (ESR), nucellus (NU), pericarp (PE), placenta-chalazal region (PC), the vascular region of the pedicel (PED), and the embryo (EMB) were isolated at 8 days after pollination (DAP) using laser-capture microdissection and sequenced using an Illumina HiSeq 2000 platform.
Publication Title
RNA sequencing of laser-capture microdissected compartments of the maize kernel identifies regulatory modules associated with endosperm cell differentiation.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
A number of macrophage and macrophage-like cells are responsible for immune response to challenges. Despite their shared role, these immune cells differ in the inflammatory response and impact on physiology and behavior. The purpose of this study was to profile mRNA levels (transcriptome) to better understand differences between immune cells under homeostasis using two mouse strains. Overall design: total RNA samples were obtained from 12 mice per strain and immune cell type and were subjected to paired-end RNA sequencing
Publication Title
Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- NextSeq 500
Description
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation. Overall design: RNA-Seq of KP-4 pancreatic adenocarcinoma cells transfected with control, BRD4 #1 or BRD4 #2 siRNA for 72hrs (n=3 independent sample preparations)
Publication Title
Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and Lysosomal Function.
Sample Metadata Fields
Specimen part, Subject
View Samples
SRP160999- Homo sapiens
- 1 Downloadable Sample
- Illumina HiSeq 3000
Description
Determine mRNA expression levels in cultured cardiomyocytes derived from human iPS cells Overall design: 1 sample
Publication Title
Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells and tumour initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-kB pathway can drive dedifferentiation of intestinal cells lacking Apc.
Publication Title
TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells and tumour initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-kB pathway can drive dedifferentiation of intestinal cells lacking Apc.
Publication Title
TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st), Illumina HiSeq 2500
Description
Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence.
Publication Title
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Sample Metadata Fields
Cell line
View Samples