This SuperSeries is composed of the SubSeries listed below.
DOCK8 is critical for the survival and function of NKT cells.
Sex, Specimen part
View SamplesAnalysis of DOCK8 deficient animals revealed a novel marker of NKT cell development, the integrin CD103. The role of CD103 was further investigated by RNA microarray comparing CD103 negative versus positive NKT cells.
DOCK8 is critical for the survival and function of NKT cells.
Sex, Specimen part
View SamplesAnalysis of DOCK8 deficient animals revealed a key role for this protein the survival and maintenance of natural killer T cells. This work lead to the identification of genes regulated by the guanine exchange factor, DOCK8.
DOCK8 is critical for the survival and function of NKT cells.
No sample metadata fields
View SamplesIL-21 induces B cell activation, and differentiation into antibody-secreting plasmablasts in vitro. This process is abolished by loss-of function mutations in STAT3
IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.
Specimen part, Disease
View SamplesDifferentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia. Overall design: We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers: CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.
Sex, Specimen part, Cell line, Subject
View SamplesAscertain the effects of disease-causing gene mutations on the differentiation status of human nave CD4+ T cells in the setting of primary immunodeficiencies. Thus, do CD4+ T cells isolated according to a nave surface phenotype (ie CD4+CD45RA+CCR7+) from healthy donors exhibit a similar gene expression profile as phenotpyically-matched cells isolated from individuals with defined primary immunodeficiencies caused by specific monogenic mutations.
Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets.
Specimen part
View SamplesGene expression studies are used to help identify disease-associated genes, by comparing the levels of expressed transcripts between cases and controls, and to identify functional genetic variants known as expression quantitative loci (eQTLs). While many of these studies are performed in blood or lymphoblastoid cell lines due to tissue accessibility, the relevance of expression differences in tissues that are not the primary site of disease is unclear. Further, many eQTLs are tissue specific. Thus, there is a clear and compelling need to conduct gene expression studies in tissues that are specifically relevant to the disease of interest. One major technical concern about using autopsy-derived tissue is how representative it is of physiologic conditions, given the effect of postmortem interval on tissue degradation.
Postmortem cardiac tissue maintains gene expression profile even after late harvesting.
Specimen part, Disease, Cell line
View SamplesComparison of the changes in mitochondrial gene expression of cells in which extracellular growth factors and/or mitogens have been added.
Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis.
Specimen part
View SamplesIn order to examine the consequences of human miR-34a induction on the transcriptome, HCT116 cells (a colon cancer cell line) were infected with a retrovirus that produces miR-34a. Gene expression profiles were then monitored using Affymetrix microarrays.
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis.
No sample metadata fields
View SamplesmRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes.
Specimen part
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