OBJECTIVE: To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS: ICR mice were food restricted by 50% from gestational days 12.5-18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured.
Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice.
Sex, Age, Specimen part
View SamplesIt has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome.
In TCR-stimulated T-cells, N-ras regulates specific genes and signal transduction pathways.
Specimen part, Treatment
View SamplesHematopoietic stem and progenitor cells are a rare, self-renewing bone marrow resident population capable of giving rise to all circulating hematopoietic cells. They can be used therapuetically for reconstituting defective or ablated hematopoietic systems following chemotherapy, and for inducing tolerance toward allografts of the same haplotype as the HSC donor. There are several sources for HSCs, such as the adult bone marrow, or umblical cord blood, which is more replete with such HSCs. However, HSCs obtained from such sources may be immunogenic, especially if isolated from adult bone marrow. To overcome this issue, our lab has establsihed human induced pluripotent stem cell-derived HPCs with the hope of creating a nonimmunogenic, readily available and unlimited source of HSCs to use for therapy.
Human iPS cell-derived hematopoietic progenitor cells induce T-cell anergy in in vitro-generated alloreactive CD8(+) T cells.
Disease
View SamplesThe cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair, cell cycle arrest and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1. Increased expression of eIF4G1, common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing autophagy and apoptosis (Survivin, HIF1, XIAP), promoting cell cycle arrest (GADD45a, p53, ATRIP, Chk1) and DNA repair (53BP1, BRCA1/2, PARP, Rfc2-5, ATM, MRE-11, others). Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to DNA damage by IR, induces cell death by both apoptosis and autophagy, and significantly delays resolution of DNA damage foci with little reduction of overall protein synthesis. While some mRNAs selectively translated by higher levels of eIF4G1 were found to use internal ribosome entry site (IRES)-mediated alternate translation, most do not. The latter group shows significantly reduced dependence on eIF4E for translation, facilitated by an enhanced requirement for eIF4G1. Increased expression of eIF4G1 therefore promotes specialized translation of survival, growth arrest and DDR mRNAs that are important in cell survival and DNA repair following genotoxic DNA damage.
DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs.
Cell line
View SamplesTranslation initiation factors have complex functions in cells which are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient-starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation and bioenergetics were selectively inhibited by reduction of eIF4GI, whereas mRNAs encoding proliferation inhibitors and catabolic pathway factors were increased. Depletion or over-expression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy and release tumor cells from control by nutrient sensing.
eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy.
No sample metadata fields
View SamplesWe established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of hexavalent chromium followed by anchorage-independent growth. The gene expression profiles were analyzed in the established cell lines.
Comparison of gene expression profiles in chromate transformed BEAS-2B cells.
Specimen part, Cell line, Treatment
View SamplesGenome-wide profiling establishes that human cytomegalovirus (HCMV) exerts an extensive, unforeseen level of specific control over which cellular mRNAs are recruited to or excluded from polyribosomes.
Global reprogramming of the cellular translational landscape facilitates cytomegalovirus replication.
Specimen part, Disease, Treatment
View SamplesTo determine early changes leading to human cell transformation (cancer) we exposed an immortalized human bronchial epithelial cell line, BEAS-2B, to one of four different metals that may cause cancer via inhalation in humans or rodents: 2.0 micro-Molar soluble sodium arsenite (NaAsO2), 0.50 micro-Molar potassium chromate (K2CrO4), 250 micro-Molar nickel (II) sulfate (NiSO4), 10 micro-Molar sodium meta-vanadate (NaVO3), or were left untreated (control). After a 30-60 day exposure, cells were rinsed of metals and seeded in soft agar. A small number of the cells formed colonies in the soft agar, demonstrating the potential for anchorage independent growth, a characteristic of cancer. These colonies that originated from a single cell were extracted from the agar and grown out in monolayer for 3-4 weeks. The RNA data provided here is taken from these cells. The significance it that the metal exposure was stopped many generations before the analysis, yet each sample demonstrates changes in gene expression based on the original metal exposure.
Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer.
Specimen part
View SamplesHuman uterine leiomyomas (ULM) are characterized by dysregulation of a large number of genes and non-coding regulatory microRNAs. In order to identify microRNA::mRNA associations relevant to ULM pathogenesis, we examined global correlation patterns between the altered microRNA expression and the predicted target genes in leiomyomas and matched myometria.
Profiling and functional analyses of microRNAs and their target gene products in human uterine leiomyomas.
Sex, Specimen part, Race
View Samples17b-Estradiol added to MEL cells expressing Gata1-ER or PU.1-ER transgenes to stimulate either erythropoietic Gata-1 dependent or myeloid PU.1 dependent gene espression in different time points
PU.1 activation relieves GATA-1-mediated repression of Cebpa and Cbfb during leukemia differentiation.
Disease, Disease stage
View Samples