3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005).
Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo.
Specimen part
View SamplesInduction of germline-competent pluripotent stem cells from mouse fibroblasts has been achieved by the ectopic expression of four genes (Oct3/4, Sox2, c-Myc and Klf4). If this method can be applied to humans for the generation of personalized human pluripotent stem cells, it would greatly facilitate the therapeutic application of stem cells by avoiding the problem of immune rejection by the recipient associated with allograft transplants. Here we show that the ectopic expression of the same four genes in human neonatal skin derived cells is sufficient to induce pluripotent stem cells indistinguishable from human embryonic stem cells in morphology, gene expression, DNA methylation, teratoma formation and long term self-renewal ability. Extensive analysis of colonies generated by ectopic expression of these four genes indicates the presence of considerable heterogeneity in the induced colonies. These results provide a new finding to generate human induced pluripotent stem cells from postnatal somatic tissues.
Heterogeneity of pluripotent marker gene expression in colonies generated in human iPS cell induction culture.
No sample metadata fields
View SamplesThe differentiation of preadipocytes into adipocytes is controlled by several transcription factors, including peroxisome proliferator-activated receptor (PPAR) and CCAAT/enhancer-binding protein (C/EBP), which are known as master regulators of adipogenesis. BCL11B is a zinc finger-type transcription factor that regulates the development of the skin and central nervous and immune systems. Here, we found that BCL11B was expressed in the white adipose tissue (WAT), particularly the subcutaneous WAT and that BCL11B/ mice had a reduced amount of subcutaneous WAT. During adipogenesis, BCL11B expression transiently increased in 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). The ability for adipogenesis was reduced in BCL11B knockdown 3T3-L1 cells and BCL11B/ MEFs, whereas the ability for osteoblastogenesis was unaffected in BCL11B/ MEFs. Luciferase reporter gene assays revealed that BCL11B stimulated C/EBP activity. Furthermore, the expression of downstream genes of the Wnt/-catenin signaling pathway was not suppressed in BCL11B/ MEFs during adipogenesis. Thus, this study identifies BCL11B as a novel regulator of adipogenesis, which works, at least in part, by stimulating C/EBP activity and suppressing the Wnt/-catenin signaling pathway.
Identification of BCL11B as a regulator of adipogenesis.
Specimen part
View SamplesDisruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion.
Cardiac Per2 functions as novel link between fatty acid metabolism and myocardial inflammation during ischemia and reperfusion injury of the heart.
Sex, Specimen part
View SamplesComparison of transcriptome between wild type, CD4 cre conditional knock-out and Bcl11b mutant mice. Overall design: Five replicates from wt newborn thymus, three replicates mutant new born thymus and four replicate of Bcl11bfl/fl: Cd4-Cre mice.
Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.
Specimen part, Cell line, Subject
View SamplesThe mammary gland of the lactating mouse synthesizes and secretes milk lipid equivalent to its entire body weight in a single 20 day lactation cycle, making it one of the most active lipid synthetic organs known. To test the hypothesis that multiple metabolic control points and potential regulatory mechanisms are involved in activating lipid and lactose synthesis at the onset of lactation we compared the mammary transcriptome of 130 genes involved in glucose metabolism between late pregnancy and early lactation and in response to dietary fat. We utilized data obtained from microarray analysis of mammary glands from quadruplicate FVB mice at pregnancy day 17, and lactation day 2. Diets containing 8% or 40% lipid were fed from lactation days 5 to 10 and mammary glands and livers of triplicate FVB mice prepared for microarray analysis. We also compared the metabolome obtained from magnetic resonance spectroscopy of flash frozen glands of the mammary gland at day 17 of pregnancy with that at day 2 of lactation. The results provide a global picture of the multiple metabolic strategies utilized to turn a quiescent organ into an incredibly efficient machine for massive but balanced lipid and lactose synthesis and implicate the transcription factor SREBP-1c in regulation of part of the pathway.
Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine.
No sample metadata fields
View SamplesBreast cancer metastases develop in the bone more frequently than any other site, and are a common cause of morbidity in the form of bone pain, pathological fractures, nerve compression, and life-threatening hypercalcemia. Despite ongoing research efforts, the molecular and cellular mechanisms that regulate breast cancer cell homing to and colonization of the bone as well as resultant pathological bone alteration remain poorly understood. To identify key mediators promoting breast cancer metastasis to bone, we utilized an immunocompetent, syngeneic murine model of breast cancer metastasis employing the mammary tumor cell line NT2.5. Following intracardiac injection of NT2.5 cells in neu-N mice, metastases developed in the bone, liver, and lung, closely mimicking the anatomical distribution of metastases in breast cancer patients. Using an in vivo selection process, we established NT2.5 sub-lines demonstrating an enhanced ability to colonize the bone and liver. Genome-wide cDNA microarray analysis comparing gene expression between parental NT2.5 cells and established sub-lines was performed.
Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2.
Specimen part
View SamplesWe used the myoma model in conjunction with gene expression profiling with microarray data as an efficient tool for high throughput analysis and to screen for differentially expressed genes. Our aim was to identify candidates playing an important role in SLPI and/or MMP-promoted tumor invasion by comparing oral carcinoma Ca9-22 cells, which highly express secretory leukocyte protease inhibitor (SLPI) gene, with SLPI-deficient Ca9-22 cells.
Human uterus myoma and gene expression profiling: A novel in vitro model for studying secretory leukocyte protease inhibitor-mediated tumor invasion.
Cell line
View SamplesVentilator induced lung injury can lead to serious conditions like ARDS which are associated with a high mortality (around 30%, Stapleton et al., Chest, 2005). We hypothesized that changes of expression levels of different genes would lead us to the identification of critical target genes, which might influence the inflammation and outcome associated with this condition.
HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the alveolar epithelium.
Disease, Cell line, Treatment
View SamplesAdenovirus infection leads to increased glycolytic metabolism in host cells. Expression of a single gene product encoded within the E4 early transcription region, E4ORF1, is sufficient to promote increased glycolytic flux in cultured epithelial cells.
Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.
Cell line
View Samples