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GSE112681
Homo sapiens
1117 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 741 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 376 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the gold standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
Publication Title
A mesenchymal stromal cell gene signature for donor age.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Although skeletal muscle cells can be generated from human iPSCs, transgene-free protocols include only limited options for their purification and expansion. In this study we found that FACS-purified myogenic progenitors generated from healthy controls and Pompe disease iPSCs can be robustly expanded as much as 5 x 1011 fold. At all steps during expansion, cells could be cryopreserved or differentiated into myotubes with a high fusion index. In vitro, cells were amenable to maturation into striated and contractile myofibers. Insertion of the acid alpha glucosidase cDNA into the AAVS1 locus in iPSCs using CRISPR/cas9 prevented glycogen accumulation in myotubes generated from a patient with classic infantile Pompe disease. In vivo, the expression of human-specific nuclear and sarcolemmar antigens indicated that myogenic progenitors engraft into murine muscle to form human myofibers. This protocol is useful for modeling of skeletal muscle disorders and for using patient-derived, gene-corrected cells to develop cell-based strategies. Overall design: Myogenic progenitors were expanded for ~15 days and harvested either in proliferation conditions or after 4 days of differentiation as described previously (van der Wal et al., 2017b). RNA was extracted using the RNeasy minikit with DNAse treatment (Qiagen, Germantown, MD). Sequencing libraries were prepared using TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, California, USA) according to the manufacturer's instructions. Libraries were sequenced on a HiSeq2500 sequencer (Illumina, San Diego, California, USA) in rapid-run mode according to the manufacturer's instructions. Reads 50 base-pairs in length were generated. The RNA-sequencing datasets listed in table S3 were downloaded and aligned with the datasets generated in this study using the 'new Tuxedo' pipeline (Pertea et al., 2016). The processed data file includes the analysis of 30 additonal Samples from other research groups, partly from GEO and partly from other sources such as ENCODE and ENA. The header table linked below lists the origin of the other Samples.
Publication Title
Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- NextSeq 500
Description
To understand organ function it is important to have an inventory of the cell types present in the tissue and of the corresponding markers that identify them. This is a particularly challenging task for human tissues like the pancreas, since reliable markers are limited. Transcriptome-wide studies are typically done on pooled islets of Langerhans, which obscures contributions from rare cell types and/or potential subpopulations. To overcome this challenge, we developed an automated single-cell sequencing platform to sequence the transcriptome of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors, a subpopulation of REG3A-positive acinar cells, and cell surface markers that allow sorting of live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus. Overall design: Islets of Langerhans were extracted from human cadaveric pancreata and kept in culture until single-cell dispersion and FACS sorting. Single-cell transcriptomics was performed on live cells from this mixture using an automated version of CEL-seq2 on live, FACS sorted cells. The StemID algorithm was used to identify clusters of cells corresponding to the major pancreatic cell types and to mine for novel cell type-specific genes as well as subpopulations within the known pancreatic cell types.
Publication Title
A Single-Cell Transcriptome Atlas of the Human Pancreas.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
Publication Title
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity.
Publication Title
Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity.
Publication Title
Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
We report a simultaneous comparison of striatal mRNA levels by RNA sequencing mice with graded levels of HD-like abnormalities Overall design: Examination of 4 different mouse lines
Publication Title
Allelic series of Huntington's disease knock-in mice reveals expression discorrelates.
Sample Metadata Fields
Specimen part, Subject
View Samples