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Mus musculus
4 Downloadable Samples
NextSeq 500
Description
The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the center of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. Evolution maintained in mammals this unique palindromic arrangement suggesting that it is functionally significant. We report that deconstructing the palindromic IgH 3'RR strongly impacts its function even when enhancers are preserved. CSR and IgH transcription appear poorly dependent from the 3'RR architecture and are more or less preserved provided 3'RR enhancers are present. By contrast, an “architectural effect” significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally expose them into a functional architecture of crucial importance. Overall design: RNAseq analysis of B-cell splenocytes with (S=stimulated) or without (R=resting) LPS activation from wt, delta2leftPAL, and deltaIRIS mice.
Publication Title
Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 384 Downloadable Samples
- NextSeq 500
Description
An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this ''innate-like'' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells' peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that 'innate like' CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells Overall design: Examination of RNA-Seq count data from 96 single cells
Publication Title
Adaptive from Innate: Human IFN-γ<sup>+</sup>CD4<sup>+</sup> T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We performed microarray analysis on ISCU myopathy patient muscle biopsies to identify transcriptional modulation of pathways involved in the cellular response to Fe-S cluster deficiency.
Publication Title
Elevated FGF21 secretion, PGC-1α and ketogenic enzyme expression are hallmarks of iron-sulfur cluster depletion in human skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation profiling reveals a predominant immune component in breast cancers.
Sample Metadata Fields
Specimen part, Disease stage, Cell line, Treatment
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines.
Publication Title
Multifactorial approach to predicting resistance to anthracyclines.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known expression subtypes but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients.
Publication Title
DNA methylation profiling reveals a predominant immune component in breast cancers.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known expression subtypes but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients.
Publication Title
DNA methylation profiling reveals a predominant immune component in breast cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
CoffinLowry Syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes Rsk2, a serine/threonine kinase involved in spatial memory. We analyzed hippocampal gene expression profiles in Rsk2-KO mice to identify changes in molecular pathways.
Publication Title
Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE28426- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion.
Publication Title
Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
We analysed the transcriptional signature in endothelial cells extracted from the bone marrow of mice engrafted with human AML and compared it to the one of mice engrafted with human normal hematopoietic cells Overall design: Immunodeficient mice were transplanted with human AML cells derived from patients, or with normal human hematopoietic cells derived from cord blood. Mice were sacrificed once assessed the bone marrow engraftment, and the bones were processed to isolate endothelial cells using the CD31 marker. RNA was extracted, sequencing libraries were prepared and sequenced.
Publication Title
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples