This SuperSeries is composed of the SubSeries listed below.
The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes.
Specimen part
View SamplesWnt signal transduction during an immune response is involved in the establishment of functional CD8 T cell memory
Differences in the transduction of canonical Wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity.
Specimen part
View SamplesThe transcription factor Tcf1 plays an essential role for the development of NK cells, however, its precise role for NK cell development, maturation and function is poorly understood. Here we show that distinct domains of Tcf1 direct bone marrow progenitors towards the NK cell lineage and mediate lineage commitment and NK cell expansion, and that Tcf1 downregulation is required for terminal NK cell maturation. Impaired NK cell development in the absence of Tcf1 is explained by increased cell death due to excessive expression of Granzyme family proteins, which results in NK cell self-destruction. In addition, excessive Granzyme B expression leads to target cell induced NK cell death and consequently reduced target cell killing by NK cells lacking Tcf1. Mechanistically, Tcf1 prevents excessive Granzyme B expression by binding to a newly identified enhancer element upstream of the Granzyme B locus. These data identify an unexpected requirement to limit the expression of cytotoxic effector molecules for lymphocyte development.
The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes.
Specimen part
View SamplesMitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Cell line, Treatment
View SamplesNon-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype.
Molecular classification of basal cell carcinoma of skin by gene expression profiling.
Sex, Specimen part
View SamplesTranscriptional comparison of developing grains between two wheat genotypes with contrasting levels of minerals in grain, using Affymetrix GeneChip Wheat Genome Array.
Comparative transcriptional profiling of two wheat genotypes, with contrasting levels of minerals in grains, shows expression differences during grain filling.
Specimen part
View SamplesThe wider transcriptional effects of MYD88L265P were explored by analysing the microarray datasets using the limma package. We focussed on evidence for differential expression between Myd88L265P and Card11L232LI transduced B cells because both cell populations were actively proliferating at the time of RNA isolation.
Synergistic cooperation and crosstalk between <i>MYD88<sup>L265P</sup></i> and mutations that dysregulate CD79B and surface IgM.
Specimen part
View SamplesMany cancer cells require more glycolytic adenosine triphosphate production due to a mitochondrial respiratory defect. However, the roles of mitochondrial defects in cancer development and progression remain unclear. To address the role of transcriptomic regulation by mitochondrial defects in liver cancer cells, we performed gene expression profiling for three different cell models of mitochondrial defects: cells with chemical respiratory inhibition (rotenone, thenoyltrifluoroacetone, antimycin A, and oligomycin), cells with mitochondrial DNA depletion (Rho0), and liver cancer cells harboring mitochondrial defects (SNU354 and SNU423). By comparing gene expression in the three models, we identified 10 common mitochondrial defectrelated genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. The concomitant expression of the 10 common mitochondrial defect genes is significantly associated with poor prognostic outcomes in liver cancers, suggesting their functional and clinical relevance. Among the common mitochondrial defect genes, we found that nuclear protein 1 (NUPR1) is one of the key transcription regulators. Knockdown of NUPR1 suppressed liver cancer cell invasion, which was mediated in a Ca2+ signalingdependent manner. In addition, by performing an NUPR1-centric network analysis and promoter binding assay, granulin was identified as a key downstream effector of NUPR1. We also report association of the NUPR1granulin pathway with mitochondrial defectderived glycolytic activation in human liver cancer. Conclusion: Mitochondrial respiratory defects and subsequent retrograde signaling, particularly the NUPR1granulin pathway, play pivotal roles in liver cancer progression.
Identification of a mitochondrial defect gene signature reveals NUPR1 as a key regulator of liver cancer progression.
Specimen part
View SamplesMammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray.
The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Sex, Age, Specimen part
View Samples