Background: Ion channels are key determinants for the function of excitable cells but little is known about their role and involvement during cardiac development. Earlier work identified Ca2+-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here, we have investigated their impact on the differentiation of pluripotent cells towards the cardiac lineage. Methods and Results: We have applied the SKCa-activator EBIO on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa-activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation and diminished teratoma formation. Time-restricted SKCa-activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the EBIO-induced effects.
Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells.
Specimen part, Cell line
View SamplesAnalysis of the transcriptome of zebrafish mononuclear myogenic cells (zMNCs) during myogenic differentiation. The main goal is to identify the similarities of zMNC myogenic differentiation with that of mammalian myoblast differentiation. Critical time points were used to identify a switch from the activity of cell proliferation genes to myogenic structural genes.
Isolation and transcriptome analysis of adult zebrafish cells enriched for skeletal muscle progenitors.
Specimen part, Time
View SamplesDespite advances in investigating functional aspects of osteoblast (OB) differentiation, especially studies on how bone proteins are deposited and mineralized, there has been little research on the intracellular trafficking of bone proteins during OB differentiation. Collagen synthesis and secretion is markedly upregulated upon Ascorbic Acid (AA) stimulation. Understanding the mechanism by which collagen is mobilized in specialized OB cells is important for both basic cell biology and diseases involving defects in bone secretion and deposition. RabGTPases are major regulators on protein trafficking throughout the cell. In this study, we identified the Rab GTPases that are upregulated during 5-day AA differentiation of OBs using microarray analysis, namely Rab1, Rab3d and Rab27b.
Rab GTPase mediated procollagen trafficking in ascorbic acid stimulated osteoblasts.
Specimen part, Cell line
View SamplesExtracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract on the ER+ breast cancer MCF-7 cells at transcriptional level in comparision to 17beta-estradiol and the ER antagonist tamoxifen. With the extract 431 genes were regulated more than 1.5 fold. The overall expression pattern differed from those of 17-estradiol or the estrogen receptor antagonist tamoxifen. We observed an enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, together with an increase of mRNAs coding for gene products involved in several stress response pathways. Regulated genes of these functional groups were highly overrepresented among all regulated genes. Various transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated.
Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.
No sample metadata fields
View SamplesTime series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision.
Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.
Subject
View SamplesWe have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin for 3 or 6 hours to induce the p38/MAP kinase pathway. In order determine transcriptional effects dependent on MSK1/2 kinase activity, H89 inhibitor was used in the study. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 3 h or 6h (in duplicates) either with or without 15-min pre-treatment with MSK1/2 inhibitor H89 (10 uM). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
No sample metadata fields
View SamplesStress induces undifferentiated stem cells to differentiate in a way that looks like normal differentiation
Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation.
No sample metadata fields
View SamplesProducts derived from roots of Leuzea carthamoides DC. (maral root) are being promoted as anti-aging and adaptogenic. The phytoecdysteroids are considered as active principles with numerous beneficial effects, but little is known about the pharmacological properties of Leuzea extracts. We, therefore, investigated the effects of a lipophilic Leuzea root extract on ER+ breast cancer MCF-7 cells at transcriptional level in comparison to 17beta-estradiol and the ER antagonist tamoxifen. With the extract 241 genes were regulated more than 1.5 fold. We observed gene regulation in an anti-proliferative and pro-apoptotic manner.
Effects of Leuzea carthamoides on human breast adenocarcinoma MCF-7 cells determined by gene expression profiling and functional assays.
No sample metadata fields
View SamplesWe have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin to induce the p38/MAP kinase pathway. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 1 h (in duplicates). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
No sample metadata fields
View SamplesA randomized, open-label, multicenter, phase II trial (NCT00455533) enrolled previously untreated women with histologically-confirmed primary invasive breast adenocarcinoma (T23, N03, M0, tumor size 2.0 cm), regardless of hormone receptor or HER2 expression status. Patients received sequential neoadjuvant therapy starting with 4 cycles of AC (doxorubicin 60 mg/m2 intravenously and cyclophosphamide 600 mg/m2 intravenously) given every 3 weeks, followed by 1:1 randomization to either ixabepilone (40 mg/m2 3-hour infusion) every 3 weeks for 4 cycles, or paclitaxel (80 mg/m2 1-hour infusion) weekly for 12 weeks.
Biomarker analysis of neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or Paclitaxel in early-stage breast cancer.
Sex, Age
View Samples