Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression. Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis. Overall design: Three biological replicates of cells treated with siRNA against Anillin or a non-targeting control are FACS sorted into 2N or 4N populations and assessed for gene expression differences via RNA Seq for a total of 12 samples.
Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53.
Cell line, Subject
View SamplesCompares shFOXO4 vs. Control in LNCaP grown in culture, or in nude mice as primary orthotopic tumors or lymph node metastases
A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer.
Specimen part
View SamplesBaseline gene expression of adipose stem cell derived iPSCs generated by lentiviral Yamanaka 4 factors. We used microarrays to analyze the global gene expression of hACS derived iPSCs with KMOS and KMOS+miR-302.
MicroRNA-302 increases reprogramming efficiency via repression of NR2F2.
Specimen part
View SamplesThe Fra-1 transcription factor promotes tumor cell growth, invasion and metastasis. While characterizing five breast cancer cell lines derived from primary human breast tumors, we identified BRC-31 as a novel basal-like cell model that expresses elevated Fra-1 levels. BRC-31 cells display elevated FAK, SRC and ERK2 phosphorylation relative to luminal breast cancer models. Inhibition of this signaling axis, through the use of pharmacological inhibitors, reduces the phosphorylation and stabilization of Fra-1. Elevated integrin V3 expression in these cells suggested that integrin receptors might activate this FAK-SRC-ERK2 signaling axis to enhance Fra-1 phosphorylation. These cells also express high levels of uPAR, a GPI-anchored receptor that has been shown to enhance integrin-mediated signaling initiated by Vitronectin engagement. Transient knockdown of uPAR in BRC31 cells grown on Vitronectin reduces Fra-1 phosphorylation and stabilization and uPAR and Fra-1 are required for Vitronectin-induced cell invasion. In clinical samples, a molecular component signature consisting of Vitronectin-uPAR-uPA-Fra-1 predicts poor overall survival in patients with breast cancer and correlates with a Fra-1 transcriptional signature. Taken together, we have identified a novel-signaling axis that leads to phosphorylation and stabilization of Fra-1, a transcription factor that is emerging as an important modulator of breast cancer progression and metastasis.
Integrin-uPAR signaling leads to FRA-1 phosphorylation and enhanced breast cancer invasion.
Age, Disease, Disease stage
View SamplesTo elucidate the gene expression footprint of antigenically challenged T-cells which had been treated with anti-LFA-1, CTLA4Ig, anti-CD40-ligand antibodies, we performed microarray gene expression analysis comparing the expression profile of costimulatory blockade treated and untreated responder T-cells.
Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells.
Specimen part
View SamplesCotton fiber were used for the expression analysis at different developmental stages
Transcriptome dynamics during fibre development in contrasting genotypes of Gossypium hirsutum L.
No sample metadata fields
View SamplesMicroglia-like cells and neural cells were generated from several hES and hIPS lines. As subset was characterized by RNA seq and compared to expression profiles of published primary and induced samples. ABSTRACT: Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages which have been recognized to play a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and Adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts and resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines, and find that pMGLs derived from MeCP2 mutant hES cells are smaller than their isogenic controls. We further describe a culture platform to study integration and live behavior of pMGLs in organotypic 3D-cultures. This modular differentiation system allows the study of microglia in highly defined conditions, as they mature in response to developmentally relevant cues, and provides a framework to study the long-term interaction of microglia residing in a tissue-like environment. Overall design: Individual donors/genetic backgrounds. Dataset inlcudes 4 differentiated neural progenitor biological replicates (NPC1-4), 2 primary fetal microglia samples as reference, 5 induced microglia samples grown in basal medium (pMGL1-5), 3 induced microglia samples grown in neural conditioned medium (pMGL1-3+NCM)
Efficient derivation of microglia-like cells from human pluripotent stem cells.
Subject
View Samplesmicroarray was done on Heart tissue from ko and wt
Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.
No sample metadata fields
View SamplesMicroglia are the resident myeloid-lineage cells in the central nervous system. Despite myriad observations of microglia associated with various tissue pathologies in degenerative disease, their function in and contributions to the pathophysiological processes remain unclear. It is particularly uncertain whether microglia act harmfully to contribute to worsening of degeneration, act beneficially to combat disease-related dysfunction, or perform functions that result in both outcomes. In this dataset, we report RNA sequencing results from mice that undergo inducible ALS/FTLD-like degeneration and subsequent recovery. The goals were to identify whether microglia show transcriptional signatures commensurate with the disease stage or if they remain constant throughout. Additionally, we sought to understand whether there was a particular transcriptional or functional signature associated with functional recovery in the mice. The latter could lead to an understanding of how microglia may be targeted to combat disease and enhance recovery following or during degeneration. Overall design: mRNA profiles from microglia sorted from whole-spinal cord taken from doxycycline (DOX) inducible NEFH-tTa/tetO-208-hTDP43 (rNLS8, (+/+)) mice. In these mice, removal of doxycycline from the diet (DOX-OFF) induces transgenic expression and degeneration and reintroduction (DOX-ON) suppresses expression and enables recovery. We report profiles from rNLS8 mice that were DOX-OFF for 2 weeks (N=8) or 6 weeks (N=7), or DOX-OFF for 6 weeks followed by DOX-ON for 1 week (N=9). We also report profiles from control samples that include: rNLS8 mice that were DOX-ON for 6 weeks (N = 6) as asymptomatic genetic controls and WT (-/-) littermates that were DOX-OFF for 2 weeks (N=4), 6 weeks (N=1), or DOX-OFF for 6 weeks followed by 1 week DOX-ON (N=3) as asymptomatic doxycycline controls.
Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy.
Sex, Specimen part, Cell line, Subject
View SamplesIntranasal (IN) immunization induces different genotype expression in CD8 memory T cells compared to the CD8 memory T cells induced by intramuscular (IM) immunization. We used microarrays to detail the global program of gene expression underlying the differential induction after IN or IM immunization.
Induction of resident memory T cells enhances the efficacy of cancer vaccine.
Specimen part, Treatment
View Samples