Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 and CD8 T cells isolated from individuals with latent tuberculosis, as well as from tuberculosis negative healthy controls. Overall, we found specific gene signatures in each cell subset that could successfully discriminate between individuals with latent tuberculosis and healthy controls. Overall design: RNA-sequencing of sorted memory CD4 and CD8 T cells from cryopreserved PBMC of 10 subjects with latent tuberculosis infection and 10 tuberculosis negative healthy controls
Circulating T cell-monocyte complexes are markers of immune perturbations.
Disease, Disease stage, Subject
View SamplesBreast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells, are thought to be responsible for metastasis and chemoresistance.. In this study, based on whole transcriptome analysis from putative breast CSCs and reverse-engineering of transcription control networks, we were able to identify two networks associated to this phenotype.
Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.
Age, Disease stage
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Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
Specimen part, Disease, Cell line
View SamplesSoft tissue sarcomas are aggressive mesenchymal cancers that affect more than 10,600 new patients per year in the US, about 40% of whom will die of their disease. Soft tissue sarcomas exhibit remarkable histologic diversity, with more than 50 recognized subtypes, but our knowledge of their genomic alterations is limited. Here we describe the results of an integrative analysis of DNA sequence, copy number, and mRNA expression in 207 samples encompassing seven major subtypes. Genes mutated in more than 5% of samples within a subtype were KIT (in gastrointestinal stromal cell tumors, or GISTs), TP53 (pleomorphic liposarcomas), PIK3CA (myxoid/round-cell liposarcoma), and NF1 (both myxofibrosarcoma and pleomorphic liposarcoma). We show evidence that PIK3CA mutations, found in 18% of myxoid/round-cell liposarcomas, activate AKT in vivo and are associated with poor outcomes. Point mutations in the tumor suppressor gene NF1 were discovered in both myxofibrosarcomas and pleomorphic liposarcomas, while genomic deletions were observed in all subtypes at varying frequencies. Finally, we found that short hairpin RNA-based knockdown of a subset of genes that are amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields the most detailed map of molecular alterations across diverse sarcoma subtypes to date and provides potential subtype-specific targets for therapy.
Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
Specimen part, Disease
View SamplesTransplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the effective dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4C, 10M dmPGE2, 60 minutes). Incubation conditions were identified (37C, 10M dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part
View SamplesPoly(A) enriched RNA derived from the L5 DRG 7 days following L5-SNT and from naïve L5-DRG tissue was subjected to RNA-seq analysis at different sequencing depths Overall design: 6 biological replicates (3 case – SNT subjected L5-DRG tissue, 3 control – naïve L5-DRG tissue). Each biological replicate was divided B46into 3 technical replicates; each of the technical replicates for a given sample was sequenced to a depth of 17M, 25M or 50M reads. Reads were single stranded and 34bps in length. Multiplexing was used in order to generate the read depths of different sizes. The gene expression values and fold changes in expression between naive and SNT samples were compared to those generated by a microarray experiment carried out on further technical replicates of the same samples, details in the manuscript (submitted - under revision).
A comparison of RNA-seq and exon arrays for whole genome transcription profiling of the L5 spinal nerve transection model of neuropathic pain in the rat.
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