The objective is to relate changes in expression of DOR/TRP53INP2, a factor involved in thyroid hormone action and autophagy, to body composition in mice fed a fat (FD) or high fat diet (HFD) for 8 days and in a genetically obese mouse model.
Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues.
Sex, Age, Specimen part
View SamplesAdipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs.
Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
Age, Specimen part
View SamplesChemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment.
Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML) patients treated with chemotherapy.
No sample metadata fields
View SamplesIn animal gonads, 23-30nt long PIWI interacting RNAs (piRNAs) guarantee genome integrity by guiding the sequence specific silencing of selfish genetic elements such as transposons. Two major branches of piRNA biogenesis, namely primary processing and ping-pong amplification, feed into the PIWI clade of Argonaute proteins. Despite our conceptual understanding of piRNA biogenesis, major gaps exist in the mechanistic understanding of the underlying molecular processes as well as in the knowledge of the involved players. Here, we demonstrate an essential role for the female sterility gene shutdown in the piRNA pathway. Shutdown, an evolutionarily conserved co-chaperone of the immunophilin class is the first piRNA biogenesis factor that is essential for all primary and secondary piRNA populations in Drosophila. Based on these findings, we define distinct groups of piRNA biogenesis factors and reveal the core concept of how PIWI family proteins are hard-wired into piRNA biogenesis processes. Overall design: small-RNA libraries from 2 control samples and 7 knock-down samples of D. mel. ovaries and 2 small-RNA profiles from Piwi IP and Aub IP from OSCs.
The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila.
Specimen part, Subject
View SamplesIt is often overlooked that human ESCs are generated from in vitro cultured, often surplus/discard, embryos considered unsuitable for transfer in infertility clinics. In vitro culture of preimplantation embryos has been associated with a number of perturbations, including ultrastructure, gene expression, metabolism and post-transfer development. We report here the transcriptional profiles characteristic of ESC lines generated from either in vitro cultured or in vivo derived embryos.
Transcriptional differences between rhesus embryonic stem cells generated from in vitro and in vivo derived embryos.
Specimen part
View SamplesLacciac Acid A was indentified as an inhibitor of DMNT1. MCF-7 cells were treated with Lacciac Acid A (200 uM) for 5 days. Changes in gene expression were identified by using Affymetrix Human gene ST1.0 arrays. We used microarrays to determine global changes in gene expression upon treatment with Lacciac Acid A an inhibitor of DMNT1.
Laccaic acid A is a direct, DNA-competitive inhibitor of DNA methyltransferase 1.
Specimen part
View SamplesIn Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis. Overall design: small RNA libraries were prepared from Piwi immuno-precipitates of five different genotypes
An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila.
Subject
View SamplesWe compared four transcription factor knockdowns using transgenic RNAi expressed in the larval fat body. FOXO, Tfb1, p53, and Stat92E-dependent gene expression in the Drosophila fat body was quantified on control and high-sugar diets in order to generate expression profiles via RNA-seq. These expression data were used to build a gene regulatory network to predict novel roles for these and other genes during caloric overload. Overall design: Control and fat body-expressed transcription factor RNAi Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M or 1M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sex, Specimen part, Treatment, Subject
View SamplesAging is a complex process characterized by a progressive decline in physiological integrity that leads to impaired cellular and tissue function. Adult stem cells play a critical role in organismal health and aging. Their age-related deterioration contributes to a reduced homeostatic and regenerative capacity. Notably, most studies of stem cell aging focus on the mechanisms of replicative aging in stem cells with high cellular turnover. Yet, the therapeutic potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASC), is increasingly recognized as potentially superior. The mechanism of aging in low turnover stem cells is thought to differ from those with high turnover and to more closely reflect chronological aging. The latter, however, is exceedingly difficult to study in slowly replicating primary human stem cells and thus remains poorly understood. Here, we employ our unique model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks in early chronological aging using RNA-seq analyses. Our findings demonstrate that the transcriptome of aging ASCs is more stable than that of age-matched fibroblasts. Limited transcriptional modifications in aging ASCs reveal more active transcriptional profiles of cell cycle genes and translation initiation genes when compared with aging differentiated cells. Accordingly, nascent protein synthesis, measured by incorporation of op-puromycin, is increased in ASCs from older individuals, concurrent with a decreased phosphorylation at ser-51 of eIF2, a mechanism of inhibiting translation initiation. A shortened G1 phase observed in the old ASCs could be linked to the increased protein synthesis activity, potentially resulting in more active cell proliferation. This effect, however, is not detected in aging fibroblasts. The altered regulation of cell cycle in aging ASCs could allow a more active cell proliferation to meet an increase demand to preserve tissue and organ functions. These observations are consistent with data supporting the maintenance of ASC integrity in aging human adipose tissue and reveal early chronological aging mechanisms in ASCs that are inherently different from other cell types. Overall design: Examination of the transcriptome with RNA-seq in stem cells and fibroblasts
Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.
Age, Specimen part, Cell line, Subject
View SamplesRetinoic acid receptors (RARs) , , and heterodimerize with Retinoid X receptors (RXR) , , and and bind the cis-acting response elements known as RAREs to execute the biological functions of retinoic acid during mammalian development. RAR mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells. Furthermore, ablation of RAR enhanced the tumor incidence of Ras transformed keratinocytes and was associated with resistance to retinoid mediated growth arrest and apoptosis.
RARγ is essential for retinoic acid induced chromatin remodeling and transcriptional activation in embryonic stem cells.
Specimen part, Treatment, Time
View Samples