Differential gene expression profiling in KMT2D-depleted MIA PaCa-2 cells was performed using Human Genome U133 Plus 2.0 Array
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.
Treatment
View SamplesThe new official nomenclature subdivides human monocytes into three subsets, classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical (CD14+CD16+). Here, we comprehensively define relationships and unique characteristics of the three human monocyte subsets using microarray and flow cytometry analysis. Our analysis revealed that the intermediate and nonclassical monocyte subsets were most closely related. For the intermediate subset, majority of genes and surface markers were expressed at an intermediary level between the classical and nonclassical subset. There features therefore indicate a close and direct lineage relationship between the intermediate and nonclassical subset. From gene expression profiles, we define unique characteristics for each monocyte subset. Classical monocytes were functionally versatile, due to the expression of a wide range of sensing receptors and several members of the AP-1 transcription factor family. The intermediate subset was distinguished by high expression of MHC class II associated genes. The nonclassical subset were most highly differentiated and defined by genes involved in cytoskeleton rearrangement that explains their highly motile patrolling behavior in vivo. Additionally, we identify unique surface markers, CLEC4D, IL-13RA1 for classical, GFRA2, CLEC10A for intermediate and GPR44 for nonclassical. Our study hence defines the fundamental features of monocyte subsets necessary for future research on monocyte heterogeneity.
Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets.
Specimen part, Subject
View SamplesFBXW7 modulates stress response by post-translational modification of HSF1 HSF1 orchestrates the heat-shock response upon exposure to heat stress and activates a transcriptional program vital for cancer cells. Genes positively regulated by HSF1 show increeased expression during heat shock while their expression is reduced during recovery. Genes negatively regulated by HSF1 show the opposite pattern. In this study we utilized the HCT116 FBXW7 KO colon cell line and its wild type counterpart to monitor gene expression changes during heat shock (42oC, 1 hour) and recovery (37oC for 2 hours post heat shock) using RNA sequencing. These results revealed that the heat-shock response pathway is prolonged in cells deficient for FBXW7. Overall design: Whole RNA was extracted from 1 million HCT116 WT or FBXW7KO cells using the RNAeasy kit (Qiagen) according to the manufacturer’s protocol. Poly-A+ (magnetic oligodT-containing beads (Invitrogen)) or Ribominus RNA was used for library preparation. cDNA preparation and strand-specific library construction was performed using the dUTP method. Libraries were sequenced on the Illumina HiSeq 2000 using 50bp single-read method. Differential gene expression analysis was performed for each matched recovery versus heat-shock pairs, separately in each biological replicate and cell line (WT or KO). Two types of comparisons were tested: (a) WT recovery vs WT heat shock, (b) FBXW7 KO recovery vs heat shock.
FBXW7 modulates cellular stress response and metastatic potential through HSF1 post-translational modification.
No sample metadata fields
View SamplesWe generated de novo induced pluripotent stem cells (iPSCs) from two Parkinson’s Disease patients (PD) harboring the p.A53T mutation. iPSC-derived mutant neurons displayed disease-relevant phenotypes at basal conditions, including protein aggregation, compromised neuritic outgrowth and contorted axons with swollen varicosities containing aSyn and tau. We have performed RNA Sequencing (RNA-Seq) of neurons from PD patient and control samples. RNA sequencing has also been performed to neurons derived from HUES samples subjected to the same differentiation protocol as reference. Overall design: We have performed RNA Sequencing (RNA-Seq) in neurons PD and control samples (two clones from each individual), along with HUES-derived neurons.
Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease.
Specimen part, Subject
View SamplesSomatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) represent two major approaches for somatic cell reprogramming. However, little attention has been paid to the ability of these two strategies in rejuvenating cells from donors with aging associated syndrome. Here, we utilized telomerase deficient (Terc-/-) mice to probe this question. SCNT-derived embryonic stem cells (ntESCs) and iPSCs were successfully derived from second generation (G2) and third generation (G3) of Terc-/- mice, and ntESCs showed better differentiation potential and self-renewal ability. Telomeres lengthened extensively in cloned embryos while remained or slightly increased in the process of iPSCs induction. Furthermore, G3 ntESCs exhibited improvement of telomere capping function as evidenced by decreased signal free ends and chromosome end-to-end fusion events. In contrast, there was a further decline of telomere capping function in G3 iPSCs. In addition to telomere dysfunction, mitochondria function was severely impaired in G3 iPSCs as evidenced by oxygen consumption rate (OCR) decline, reactive oxygen species (ROS) accumulation and dramatically increased mitochondria genome mutations while these deficiencies were greatly mitigated in G3 ntESCs. Our data proved the principle that SCNT-mediated reprogramming appears more superior than transcription factors induced reprogramming in terms of the resetting of telomere quality and mitochondria function, and thus, providing valuable information for further improvement of transcription factors mediated reprogramming.
Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells.
Specimen part
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MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene.
Sex, Age, Specimen part, Cell line
View SamplesThe study of mammalian development has offered many insights into the molecular aetiology of cancer. We previously used analysis of mammary morphogenesis to discover a critical role for GATA-3 in mammary developmental and carcinogenesis. In recent years an important role for MicroRNAs (miRNAs) in a myriad of cellular processes in development and in oncogenesis has emerged. In this study, microRNA profiling of stromal and epithelial cellular subsets microdissected from the developing mouse mammary gland revealed many microRNAs with expression restricted to various cellular subsets. MicroRNA-184 (miR-184) was exclusively expressed in epithelial cells and markedly upregulated during differentiation of the proliferative, invasive cells of the pubertal terminal end bud (TEB) into ductal epithelial cells in vivo and in FACS-sorted mammary stem cells (MaSCs) versus luminal epithelial cells. miR-184 expression was silenced in mouse tumour models compared to non-transformed epithelium and in a majority of breast cancer cell line models. Ectopic reactivation of miR-184 inhibited the proliferation and self-renewal of metastatic triple negative breast cancer (TNBC) cell lines in vitro and delayed tumour formation and reduced metastasis in vivo. Gene expression studies uncovered multi-factorial direct regulation of genes in the AKT/mTORC1 pathway by miR-184. In clinical breast cancer tissues, expression of miR-184 is lost in primary TNBCs while the miR-184 promoter is methylated in a subset of lymph node metastases from TNBC patients. These studies elucidated a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour proliferation and metastasis.
MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene.
Sex, Specimen part, Cell line
View SamplesDownsream of GRID2 in the mouse cerebellum.
Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line.
Sex, Age
View SamplesObjective: Transcriptional profiling of murine HSPC in response to ß-glucan-induced innate immune training Overall design: HSPC mRNA profiles of wild type (WT) mice injected with PBS or ß-glucan. Wild type (WT) C57BL/6 mice were intraperitoneally injected with PBS or 1 mg ß-glucan in PBS. Mice were sacrificed on day 7 or day 28 and long-term heematopoietic stem cells (LT-HSC) and/or multipotent progenitors (MPP) were sorted. In another group, mice were injected with PBS or 1 mg ß-glucan in PBS and on day 7 they were additionally injected with 150 mg/kg 5-fluouracil. Mice were sacrificed on day 14 after 5-FU administration and LT-HSC were sorted.
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.
Age, Specimen part, Cell line, Subject
View SamplesTightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Overall design: Comparison of gene expression at different stages of keratinocyte differentiation
Genome-wide p63-regulated gene expression in differentiating epidermal keratinocytes.
No sample metadata fields
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