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SRP173201
Mus musculus
8 Downloadable Samples
Illumina HiSeq 4000
Description
Purpose: to identify the effects of the Dp1Tyb mutation on the transcriptome of mouse embryonic fibroblasts Overall design: RNAseq libraries were prepared from RNA isolated from mouse embryonic fibroblasts. Libraries were prepared from total RNA using the TruSeq Stranded mRNA Sample Prep Kit (Illumina) by the Advanced Sequencing Facility, The Francis Crick Institute. Libraries were sequenced (100 bases paired end) on the Illumina Hiseq 4000 Please note that this dataset contains ERCC spike ins to normalise the data
Publication Title
Gene expression dysregulation domains are not a specific feature of Down syndrome.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 94 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically-pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether transgenic modification of the cell cycle results in secondary effects that could undermine the validity of these cell models. Here we subjected healthy and disease lines to intensive transcriptomic analysis, comparing immortalized lines with their parent primary populations in both differentiated and undifferentiated states, and testing their myogenic character by comparison with non-myogenic (CD56-negative) cells. We found that immortalization has no measurable effect on the myogenic cascade or on any other cellular processes, and that it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells.
Publication Title
Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Here we demonstrate ALK3Bright/PDX1+ cells residing within the human pancreatic ducts have progenitor like characteristics. Using flow cytometery, live-cell sorting of ALK3bright/PDX1+ cells is possible using a surrogate surface marker for PDX1 (P2RY1). Treating ALK3bright/P2RY1+ cells with BMP7 results in their expansion. Later removal of BMP7 results in the differentiation of these cells to ß-like cells. Here we compare the mRNA expression profiles of these three different cell types (in triplicate). Methods: mRNA profiles of ALK3Bright/P2RY1+ cells isolated from human non-endocrine pancreatic tissue, ALK3Bright/P2RY1+ cells treated with BMP7 and ALK3Bright/P2RY1+ cells differentiated to ß-like cells after BMP7 removal were generated by deep sequencing, in triplicate, using Illumina HiSeq PE Cluster Kit v4 and Illumina HiSeq Flow Cell v4 with 50 nt paired end reads plus dual index reads using the Illumina HiSeq SBS kit v4. Sequence reads that passed quality filters were analyzed at the transcript isoform level following alignment using TopHat v2.1.0 followed by exon and gene level counting using Bioconductor easyRNASeq v 2.4.7. Conclusions: Our study represents the first detailed analysis of ALK3Bright/P2RY1+ sorted cells with biological replicates. We demonstrate ALK3Bright/P2RY1+ cells were shown to form progenitor-like epithelial colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies responded to BMP-7 by generating new ß-like cells as well as cells from other pancreatic lineages. The transcriptional profile of these cells and their BMP7 treated counterparts suggest a mitotic and progenitor like state. Our studies confirm the progenitor-like nature of ALK3Bright/PDX1+ cells within the human pancreas and suggest a specific anatomical location within the ductal network. Overall design: Comparison of transcriptional expression in Alk3Bright/P2RY1+ cells, Alk3Bright/P2RY1+ cells treated with BMP7 and Alk3Bright/P2RY1+ cells allowed to differentiate after BMP7 removal. Human islets, isolated from the same donors were included as a control.
Publication Title
P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Natural Killer (NK) cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantations (h-HSCTs) with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after h-HSCT of a donor-derived unconventional subset of CD56dim/CD16neg (uCD56dim) NK cells expressing remarkable high levels of NKG2A and low levels of NKp46. Both transcription and phenotypic profiles indicated that uCD56dim NK cells are a distinct NK cell subpopulation with features of late differentiation, yet retaining proliferative capability and functional plasticity to generate conventional CD56bright/CD16pos NK cells in response to IL-15 plus IL-18. uCD56dim NK cells represent by far the largest NK cell subset detectable in the following 7 weeks after h-HSCT and they also express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, uCD56dim NK cells displayed a defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human NK cells and to develop a novel immune-therapeutic approach by targeting the inhibitory NKG2A check point, thus enhancing NK cell alloreactivity early after h-HSCT.
Publication Title
The early expansion of anergic NKG2A<sup>pos</sup>/CD56<sup>dim</sup>/CD16<sup>neg</sup> natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The effectiveness of new cancer therapies such as checkpoint blockade and adoptive cell transfer of activated anti-tumor T cells requires overcoming immunosuppressive tumor microenvironments. We found that the activation of tumor-infiltrating myeloid cells to produce local nitric oxide is a prerequisite for adoptively transferred CD8+ cytotoxic T cells to destroy tumors. These myeloid cells are phenotypically similar to Tip-DCs or nitric oxide- and TNF-producing dendritic cells. The nitric oxide-dependent killing was tempered by coincident arginase 1 expression, which competes with iNOS for arginine, the substrate for nitric oxide production. Depletion of immunosuppressive CSF-1R-dependent arginase 1+ myeloid cells enhanced nitric oxide-dependent tumor killing. Tumor killing via iNOS was independent of the microbiota but dependent on the CD40-CD40L pathway and, in part, lymphotoxin alpha. We extended our findings in mice to uncover a strong correlation between iNOS, CD40 and TNF expression and survival in colorectal cancer patients. Our results identify a network of anti-tumor targets to boost the efficacy of cancer immunotherapies.
Publication Title
T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Among the dendritic cell (DC) subsets, plasmacytoid DCs are thought to be important in both generating antiviral and antitumor responses. These cells may be useful in developing dendritic cell-based tumor vaccines, however, the rarity of these cells in the peripheral blood have hampered attempts to understand their biology. To provide better insight into the biology of plasmacytoid DCs, we isolated these cells from the peripheral blood of healthy donors in order to further characterize their gene expression. Using gene array technology we compared the genetic profiles of these cells to those of CD14+ monocytes isolated from the same donors and found several immune related genes upregulated in this cell population. Understanding the genetic profiles of this dendritic cell subtype as well as others such as the BDCA-1 expressing myeloid DCs may enable us to manipulate these cells ex-vivo to generate enhanced DC-based tumor vaccines inducing more robust antitumor responses.
Publication Title
Genetic profiles of plasmacytoid (BDCA-4 expressing) DC subtypes-clues to DC subtype function in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pitx3 is a transcription factor that is expressed in all midbrain dopaminergic (mDA) neurons during early development, but later becomes restricted in dopaminergic subsets of substantia nigra compacta (SNc) and of the ventral tegmental are (VTA) that are vulnerable to neurodegenerative stress (MPTP, 6-OHDA, rotenone, Parkinson's disease). Overall, in mice, Pitx3 is required for developmental survival of ventral SNc neurons and for postnatal survival of VTA neurons (after postnatal day 40). With the aim of determining the gene networks that distinguish Pitx3-vulnerable (Pitx3-positive) from Pitx3-resistant (Pitx3-negative) subsets of SNc and VTA, we performed a comparison at the transcriptome level between FAC-sorted mDA neurons of SNc and VTA that were obtained from wild-type and Pitx3-/- newborn mice. The latter mice have already lost the majority of their TH+Calb1- mDA neurons of ventral SNc (Pitx3-dependent), but their TH+Calb1+ neurons of dorsal SNc (Pitx3-independent), including all of VTA neurons (50% are Pitx3-dependent and 50% Pitx3-independent), are unaffected by Pitx3 deletion. At postnatal day 40, Pitx3-/- mice display a marked loss of dopaminergic subsets of VTA that normally co-express Pitx3 and Calb1 (Pitx3-dependent neurons of VTA).
Publication Title
Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 47 Downloadable Samples
- IlluminaHiSeq2500
Description
We have discovered subsets of axon guidance molecules and transcription factors that are enriched in specific subsets of olfactory sensory neurons. We have demonstrated guidance activity for three of the candidate axon guidance genes we identified, suggesting that this approach is an efficient method for characterizing guidance systems relevant to olfactory axon targeting. Overall design: Single-cell RNASeq of OMP-expressing olfactory sensory neurons was performed by capture on Fluidigm-C1 followed by sequencing on Illumina HiSeq2500
Publication Title
Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Pseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; F508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Publication Title
Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In this study, we used the Affymetrix HG-U133A 2.0 GeneChip for deriving a multigenic classifier capable of predicting HCV+cirrhosis with vs without concomitant HCC.
Publication Title
Identifying genes for establishing a multigenic test for hepatocellular carcinoma surveillance in hepatitis C virus-positive cirrhotic patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples