We compare the transcriptome of embryonic stem cells (ESCs), adult stem cells with apparent greater differentiation potential such as multipotent adult progenitor cells (MAPCs), mesenchymal stem cells (MSCs) and neurospheres (NS). Mouse and rat MAPCs were used in this study and two different array platforms (Affymetrix and NIA) were used for mouse samples.
Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity.
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View SamplesPurpose: To evaluate the presence of a gene expression signature present before treatment as predictive of response to treatment with MAGEA3
Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy.
Specimen part
View SamplesMalignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal, survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis.
Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells.
Cell line
View SamplesBone marrow mesenchymal stem cells (MSC) were adipogenically differentiated followed by dedifferentiation. We are interested to know the new fat markers, adipogenic signaling pathways and dedifferentiation signaling pathways.Furthermore we are also intrested to know that how differentiated cells convert into dedifferentiated progenitor cells. To address these questions, MSC were adipogenically differentiated, followed by dedifferentiation. Finally these dedifferentiated cells were used for adipogenesis, osteogenesis and chondrogenesis. Histology, FACS, qPCR and GeneChip analyses of undifferentiated, adipogenically differentiated and dedifferentiated cells were performed. Regarding the conversion of adipogenically differentiated cells into dedifferentiated cells, gene profiling and bioinformatics demonstrated that upregulation (DHCR24, G0S2, MAP2K6, SESN3) and downregulation (DST, KAT2, MLL5, RB1, SMAD3, ZAK) of distinct genes play a curcial role in cell cycle to drive the adipogenically differentiated cells towards an arrested state to narrow down the lineage potency. However, the upregulation (CCND1, CHEK, HGF, HMGA2, SMAD3) and downregulation (CCPG1, RASSF4, RGS2) of these cell cycle genes motivates dedifferentiation of adipogenically differentiated cells to reverse the arrested state. We also found new fat markers along with signaling pathways for adipogenically differentiated and dedifferentiated cells, and also observed the influencing role of proliferation associated genes in cell cycle arrest and progression.
Transdifferentiation of adipogenically differentiated cells into osteogenically or chondrogenically differentiated cells: phenotype switching via dedifferentiation.
Specimen part
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesThe R47H variant of TREM2 is associated with higher risk of Alzheimer's disease. We generated mice expressing the common variant or R47H variant of human TREM2
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism.
Sex, Age, Specimen part
View SamplesILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6NKp46 DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear.
IL-15 sustains IL-7R-independent ILC2 and ILC3 development.
Specimen part
View SamplesThe capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival. Overall design: Haley, J.A., Haughney, E., Ullman, E., Bean, J., Haley, J.D.* and Fink, M.Y. (2014) 'Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant KRas NSCLC Models' Front. Oncology, doi/10.3389/fonc.2014.00344.
Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant-KRas NSCLC Models.
Treatment, Subject
View SamplesTo assess natural variation of downstream auxin responses we subjected 7 different arabidopsis ecotypes to a time course of auxin treatments. 7d-old seedlings grown in liquid culture have been treated for 0, 30 min, 1h and 3h with 1 M IAA.
Natural variation of transcriptional auxin response networks in Arabidopsis thaliana.
Specimen part
View SamplesWe used microarrays to compare gene expression between three HRAS-wild type lines (13, 162d, 165d) and three HRAS-G12S mutant lines (7, 8, 16).
Dysregulation of astrocyte extracellular signaling in Costello syndrome.
Specimen part
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