This SuperSeries is composed of the SubSeries listed below.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
View SamplesThe effect of different loss of functions; kumgang (kmg or CG5204), dMi-2, and kmg and always early (aly) double on the gene expression in spermatocyte differentation was assessed by microarray.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
View SamplesThe innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. To understand the effect of exosomal cargo released from locally stimulated cells on distal cell expression, we collected exosomes from local ovarian adenocarcinoma (HEY) cells that were either unstimulated (control-exosomes), stimulated with pIC (pIC-exosomes), or lipopolysaccharide (LPS-exosomes) for 48 hours. The three groups of exosomes were added to nave (distal) cells and the gene expression profiles were compared between local TLR stimulation (for 6 hours) and distal stimulation mediated by exosomes at the 48-hour time point
TLR-exosomes exhibit distinct kinetics and effector function.
Specimen part, Cell line, Treatment
View SamplesTo detect sex-specific differences in gene expression in a model of hyperoxic lung injury in adult C56BL/6J mice.
Analysis of the transcriptome in hyperoxic lung injury and sex-specific alterations in gene expression.
Sex, Specimen part, Treatment
View SamplesThe Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives.
Sex, Specimen part
View SamplesOur work demonstrated that miR-183 cluster regulates IFN production and signaling
A conserved miRNA-183 cluster regulates the innate antiviral response.
Cell line
View SamplesThe nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPAR and the HS response mediated by HSF1. Wild-type and PPAR-null mice were exposed to HS, the PPAR agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPAR-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPAR-null mice that are known targets of PPARg co-activator 1 (PGC-1) family members. Pretreatment of PPAR-null mice with WY increased expression of PGC-1b and target genes and prevented the down-regulation of the mitochondrial genes by HS. A comparison of HS genes regulated in our dataset with those identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that although many HS genes are regulated independently of both PPAR and HSF1, a number require both factors for HS responsiveness. These findings demonstrate that the PPAR genotype has a dramatic effect on the transcriptional targets of HS and support an expanded role for PPAR in the regulation of proteome maintenance genes after exposure to diverse forms of environmental stress including HS.
Analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha).
Sex, Age, Specimen part
View Samples1 year old mice were perfused and brains were dissociated. Cells were fixed, immunolabeled and FACS sorted. RNA was extracted from neuron, astrocyte, and microglial cell populations. Typical RIN=4-5 for neurons, 6-8 for astrocytes, and 5-7 for microglia. Typical RNA yields ~100ng for neurons, ~20ng for microglia, and ~10ng for astrocytes. cDNA was generated from up to 25 ng of total RNA using Nugen’s RNA-Seq method for low-input RNA samples, Ovation RNA-Seq System V2 (NuGEN). (Per manufacturers instructions, total RNA was neither depleted of rRNA nor polyA-selected.) 1 µg of sheared cDNA was taken into further processing, starting at end repair step, using Illumina’s TruSeq RNA Sample Preparation Kit v2 (Illumina). The "SAMID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007717 Overall design: Astrocytes, microglia and neurons were sorted from PGRN heterozygous or knockout mice.
Progranulin deficiency causes impairment of autophagy and TDP-43 accumulation.
Sex, Specimen part, Subject
View SamplesRNA was extracted from cortex of 1 year old wildtype, heterozygous or homozygous PGRN knockout mice. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007808 Overall design: RNA was extracted from cortex of 1 year old wildtype, heterozygous or homozygous PGRN knockout mice.
Progranulin deficiency causes impairment of autophagy and TDP-43 accumulation.
Specimen part, Subject
View SamplesNaïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent Overall design: transcription profile of ESCs and EpiLCs to analzye changes during differentiation and the effect of Otx2 loss and overexpression on the differentiation properties
Reorganization of enhancer patterns in transition from naive to primed pluripotency.
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