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SRP179668
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 4000
Description
Red blood cells (RBCs) mature within a specialized niche (the erythroblastic island (EI)), which consists of a central macrophage surrounded by differentiating erythroblasts. Human Induced Pluripotent Stem Cell derived macrophages (iPSC-DMs) enhance proliferation and terminal maturation of Umbilical Cord Blood (UCB) CD34+ derived erythroid cells and iPSC derived erythroid cells. These effects are further increased when an inducible KLF1-ERT2 fusion protein is activated in iPSC-DMs. To assess the mechanism of action, we sought to compare the transcriptome of iPSC-DMs with and without KLF1 activation. For this, we used an inducible IPSC line (iKLF1.2) in which upon tamoxifen addition, the KLF1 transcription factor is translocated to nucleus and consequently KLF1 downstream targets are expressed. The identification and characterisation of could identify factors involved in erythroid maturation and thus helpful to improve current protocols to manufacture RBCs in vitro. Overall design: iKLF1.2 iPSCs were differentiated to macrophages and then split into 2 groups, one was treated with tamoxifen for the last 4 days of culture to activate KLF1. The other group was not treated with tamoxifen. Four biologically independent differentiation experiments were carried out and so 8 samples were generated: 4 samples of untreated iKLF1.2 iPSCs-derived macrophages and 4 samples of tamoxifen treated iKLF1.2 iPSC-derived macrophages. Total RNA was extracted from each sample and RNA integrity was of a high enough quality for library preparation, as all RIN values were above 9 for every sample.
Publication Title
Genetic programming of macrophages generates an in vitro model for the human erythroid island niche.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 99 Downloadable Samples
- Illumina HiSeq 2000
Description
Assessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq. Overall design: 103 total samples from 63 unique patients. Clinical details were provided only for the 50 samples in current publication. However, all 103 samples were analyzed together.
Publication Title
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.
Sample Metadata Fields
Age, Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- Illumina HiSeq 2500
Description
FSHD myoblasts show a suppression of ESRRA and PPARGC1A during myogenesis Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent, then induced to differentiate for 3.5 days, samples were taken at 8 time points during differentation for 54-6 and 54-12 and at confluency and terminal differentiation in the remaining lines. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.
Publication Title
Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
TC71 cells treated either with BEZ235 or DMSO
Publication Title
hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
Pluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. Overall design: RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.
Publication Title
Zfp281 Coordinates Opposing Functions of Tet1 and Tet2 in Pluripotent States.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.
Publication Title
The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A number of key regulators of mouse embryonic stem (ES) cell identity, including the transcription factor Nanog, show strong expression fluctuations at the single cell level. The molecular basis for these fluctuations is unknown. Here we used a genetic complementation strategy to investigate expression changes during transient periods of Nanog downregulation. Employing an integrated approach, that includes high-throughput single cell transcriptional profiling and mathematical modelling, we found that early molecular changes subsequent to Nanog loss are stochastic and reversible. However, analysis also revealed that Nanog loss severely compromises the self-sustaining feedback structure of the ES cell regulatory network. Consequently, these nascent changes soon become consolidated to committed fate decisions in the prolonged absence of Nanog. Consistent with this, we found that exogenous regulation of Nanog-dependent feedback control mechanisms produced more a homogeneous ES cell population. Taken together our results indicate that Nanog-dependent feedback loops play a role in controlling both ES cell fate decisions and population variability.
Publication Title
Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. Overall design: RNA sequencing analysis was performed in mouse embryonic stem cells with Luciferase and Tex10 knockdown. RNA-seq Experiments were carry out in two biological replicates.
Publication Title
Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung. Overall design: 24 samples, 12 iMac/iMicro, 12 BM-Mac/BM-Micro. Macrophages were analysed at 4 time points (day 0, 3, 6, 12), with 3 independent replicates for each time point. Non-cocultured samples from the same batch (Day 0 iMac/BM-Mac) were used as controls for the experiment.
Publication Title
Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples