Filters
Technology
Platform
SRP189204
Homo sapiens
19 Downloadable Samples
NextSeq 500
Description
Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects
Publication Title
Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Comparison of dorsal skin gene expression between GFP and IL-17 gene transfer in C57BL/6J mice
Publication Title
T Cell-Independent Mechanisms Associated with Neutrophil Extracellular Trap Formation and Selective Autophagy in IL-17A-Mediated Epidermal Hyperplasia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human intervention study with two doses of iron (as ferrous gluconate via intestinal perfusion) to study the effect on genome-wide gene expression in the small intestine, in order to obtain detailed information about intestinal transcriptomics in vivo.
Publication Title
Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress.
Sample Metadata Fields
Sex, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes.
Publication Title
Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT.
Publication Title
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
Sample Metadata Fields
No sample metadata fields
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
- 8 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Microglia are the brain-resident myeloid cells of the parenchyma. We study the roles microglia play in response to virus infection.
Publication Title
Microglia are required for protection against lethal coronavirus encephalitis in mice.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Hematogenous macrophages infiltrate the brain after virus infection. We use a CSF1R inhibitior, PLX5622 to deplete microglia from the brain. However, macrophages also express the CSF1R and may be affected by PLX5622-treatment of mice.
Publication Title
Microglia are required for protection against lethal coronavirus encephalitis in mice.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: CD4+ T helper cells were sorted as naive T cells (CD4+CD25-CD45RA+), Treg (CD4+CD25+IL7Rlo), Th1 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6-), Th2 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6-), Th17 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6+), Th1-17 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6+), and Tfh subsets (CXCR5+ counterparts of each). RNA-seq cDNA library construction was performed using the SMART-Seq v4 Ultra Low Input RNA Kit (Clontech) with 2?ng of input RNA. Sequencing libraries were prepared using the Nextera XT DNA Library Prep Kit (Illumina).
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: Dissociated tumor samples were sorted as either CD45+ CD3+ tumor-infiltrating T cells, other CD45+ CD3- tumor-infiltrating lymphocytes and CD45- CD3- tumor/stromal cells. Sorted cells were subjected to paired single cell RNA- and TCR-sequencing on the droplet based 10X Genomics platform.
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Sample Metadata Fields
No sample metadata fields
View Samples