The mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG)
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth.
Cell line
View SamplesThe ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice. Overall design: Whole-transcriptome profiling of the cerebral cortex of wild-type control C57BL/6J mice and two independent Plat-/- mice strains on the C57BL/6J background.
Passenger mutations and aberrant gene expression in congenic tissue plasminogen activator-deficient mouse strains.
Age, Specimen part, Cell line, Subject
View SamplesRemembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. Overall design: 3 biological replicates per group were analyzed. The material analyzed was whole hippocampi from one brain hemisphere, from which total RNA was extracted.
Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories.
No sample metadata fields
View SamplesWe are investigating the transcriptional response of yeast to treatment with enediynes or gamma radiation, which generate different extents of double or single strand breaks in DNA.
The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA.
No sample metadata fields
View SamplesWe are investigating the transcriptional response of Anc1 deficient yeast under basal and MMS exposed conditions
Anc1, a protein associated with multiple transcription complexes, is involved in postreplication repair pathway in S. cerevisiae.
No sample metadata fields
View SamplesMolecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury
Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury.
Specimen part, Disease, Time
View SamplesSingle-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on a- and ß-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between a- and ß-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 a, 105 ß, 6 d endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between a- and ß-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian ß-cells. We report on East-Asian a- and ß-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian ß-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis. Overall design: 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. 223 islet-cells remained after samples QC, and these cells were used for subsequent analyses. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. We identified 118 a and 105 ß endocrine cells in our dataset.
Single-cell transcriptomics of East-Asian pancreatic islets cells.
No sample metadata fields
View SamplesChanges in gene regulation have long been known to play important roles in both innate and adaptive immune responses. However, post-transcriptional mechanisms involved in mRNA processing have been poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Overall design: Transcriptomic profiles of 198 infected (Listeria and Salmonella) and non-infected samples at multiple time points.
Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.
Specimen part
View SamplesThe transcription factor Foxp3 is indispensable for the ability of regulatory T (Treg) cells to suppress fatal inflammation. Here, we characterized the role of Foxp3 in chromatin remodeling and regulation of gene expression in actively suppressing Treg cells in an inflammatory setting. Although genome-wide Foxp3 occupancy of DNA regulatory elements was similar in resting and in vivo activated Treg cells, Foxp3-bound enhancers were poised for repression only in activated Treg cells. Following activation, Foxp3-bound sites showed reduced chromatin accessibility and selective H3K27 tri-methylation, which was associated with Ezh2 recruitment and downregulation of nearby gene expression. Thus, Foxp3 poises its targets for repression by facilitating formation of repressive chromatin in regulatory T cells upon their activation in response to inflammatory cues.
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.
Specimen part
View Samples