Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.
Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.
Sex, Age, Specimen part
View SamplesThe goal of this experiment was to explore the molecular network of glucose-TOR signaling in Arabidopsis seedling autotrophic transition stage. We used the whole-genome microarrays to detail the global program of gene expression mediated by glucose and TOR.
Glucose-TOR signalling reprograms the transcriptome and activates meristems.
Age, Specimen part, Treatment
View SamplesThe Hematopoietically-expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of Common Lymphoid Progenitors (CLPs) to lymphoid lineages. However, whether Hhex plays a role in HSC self-renewal and myeloid expansion during hematopoietic stress is unknown. Here we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature hematopoietic progenitors. Transcriptome analysis of Hhex-null Lin-Sca+Kit+ (LSK) cells showed that Hhex deletion leads to the deregulation of Polycomb Repressive Complex 2 (PRC2) target genes, including an upregulation of Cdkn2a locus, encoding the cell cycle repressors p16Ink4a and p19Arf. Indeed, loss of Cdkn2a restored Hhex-null blast colony replating in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to repress Cdkn2a to enable continued self-renewal and response to hematopoietic stress. Overall design: Transcriptional profiling of Hhex-deleted and wild-type LSK cells using RNA sequencing
Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential innate immune signalling via Ca(2+) sensor protein kinases.
Age, Specimen part, Time
View SamplesThe eukaryotic cytoplasmic chaperonin-containing TCP-1 (CCT) is a complex formed by two back-to-back stacked hetero-octameric rings that assists the folding of actins, tubulins and other proteins in an ATP-dependent manner. Here, we decided to test the significance of the hetero-oligomeric nature of CCT for its function by introducing, in each of the eight subunits in turn, an identical mutation at a position involved in ATP binding and conserved in all the subunits, in order to establish the extent of individuality of the various subunits. Our results show that these identical mutations lead to dramatically different phenotypes. For example, cells with the mutation in CCT2 have an excess of actin patches and are the only pseudo-diploid strain. By contrast, cells with the mutation in CCT7 are the only ones to accumulate juxta-nuclear protein aggregates that may reflect the absence of stress response in this strain. System-level analysis of the strains using RNA microarrays reveals connections between CCT and several cellular networks including ribosome biogenesis and TOR2 that help to explain the phenotypic variability observed
Equivalent mutations in the eight subunits of the chaperonin CCT produce dramatically different cellular and gene expression phenotypes.
No sample metadata fields
View SamplesThe goal of this experiment was to identify the early responsive genes activated by the 22 amino acid peptide of bacterial flagellin (flg22) in Arabidopsis mesophyll cells that are involved in the initial responses important for plant innate immunity.
Differential innate immune signalling via Ca(2+) sensor protein kinases.
Age, Specimen part, Time
View SamplesThe goal of this experiment was to identify the early target genes of constitutively activated CPK5ac and CPK11ac in Arabidopsis mesophyll cells that are involved in early flagellin responses important for plant innate immunity.
Differential innate immune signalling via Ca(2+) sensor protein kinases.
Age, Specimen part
View SamplesThe goal of this experiment was to identify the early responsive genes activated by the 22 amino acid peptide of bacterial flagellin (flg22) in Arabidopsis seedlings that are involved in the initial responses important for plant innate immunity.
Differential innate immune signalling via Ca(2+) sensor protein kinases.
Age, Specimen part, Time
View SamplesTumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Specimen part, Cell line, Treatment
View SamplesIn this dataset, we include the expression data obtained from dissected mouse 16.5 embryonic brains using 3 wild type and 3 Tdp21-3 individuals. These data are used to obtain 165 genes that are differentially expressed as a consequence of Tdp2 absence.
TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.
Specimen part
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