The Endoplasmic Reticulum–Mitochondria Encounter Structure (ERMES) is a protein complex that tethers the two organelles and creates the physical basis for communication between them. ERMES functions in lipid and calcium exchange between the ER and mitochondria, mitochondrial protein import and maintenance of mitochondrial morphology and genome. Here we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of ERMES known roles in calcium regulation, phospholipid biosynthesis or mitochondrial biology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our study reveals that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels. Overall design: various mutants
Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.
Subject
View SamplesThe N-terminal tail of histone H2A shows evolutionary changes that parallel genome size and aid chromatin compaction. As genome size increases, so does the number of arginines. In contrast, serines corellate with small genomes. Examples for such changes are arginine in position 11 and serine in position 15.
Evolution of histone 2A for chromatin compaction in eukaryotes.
No sample metadata fields
View SamplesThe functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.
CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.
Specimen part, Subject
View SamplesPlants often face combinatorial stresses in their natural environment. Here arsenic (As) toxicity was combined with hypoxia (Hpx) in the roots of Arabidopsis thaliana as it often occurs in nature. The present work aimed to explore the effects of single and combined hypoxia and As stress applied at realistic stress levels to hydroponically grown A. thaliana.
Interference between arsenic-induced toxicity and hypoxia.
Specimen part
View SamplesWe report that whole body PRMT7-/- adult mice display a significant reduction in in muscle mass. RNA sequencing was performed to identify potential PRMT7 targets. We found that top canonical pathways affected by the loss of PRMT7 includes cell cycle and senescence. Overall design: RNA was extracted from tibialis anterior muscles harvested from 3 WT and 3 PRMT7 null mice at 8months. RNA sequencing was performed to compare mRNA in skeletal muscles between WT and KO mice.
PRMT7 Preserves Satellite Cell Regenerative Capacity.
Age, Specimen part, Cell line, Subject
View SamplesThere were two genotypes:
Loss of a callose synthase results in salicylic acid-dependent disease resistance.
No sample metadata fields
View SamplesDiffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult glioblastomas (GBM). Thus, we directly compared inflammatory characteristics of DIPG and adult GBM. We found that the leukocyte (CD45+) compartment in primary DIPG tissue samples is predominantly composed of CD11b+ macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant in adult GBM tissue samples. RNA sequencing of macrophages isolated from primary tumor samples revealed that DIPG- and adult GBM-associated macrophages both express gene programs related to ECM remodeling and angiogenesis, but DIPG-associated macrophages express substantially fewer inflammatory factors than their adult GBM counterparts. Examining the secretome of glioma cells, we found that patient-derived DIPG cell cultures secrete markedly fewer cytokines and chemokines than patient-derived adult GBM cultures. Concordantly, bulk and single-cell RNA sequencing data indicates low to absent expression of chemokines and cytokines in DIPG. Together, these observations suggest that the inflammatory milieu of the DIPG tumor microenvironment is fundamentally different than adult GBM. The low intrinsic inflammatory signature of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory phenotype of DIPG-associated microglia/macrophages. Understanding the glioma subtype-specific inflammatory milieu may inform the design and application of immunotherapy-based treatments. Overall design: RNA-seq of primary isolated microglia/macrophages from early post-mortem DIPG tissue samples, pediatric normal cortex, and adult GBM tissue samples. Libraries were sequenced on Illumina NextSeq 500, 1x75.
Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesTo examine the role of retinol binding protein 7 (RBP7) in PPAR gamma mediated regulation of target gene expression in the carotid artery, RNA-Seq was used to quantitate gene expression in carotid artery from both wild-type and RBP7 knockout mice after ligand-mediated activation of PPAR gamma with Rosiglitazone. Overall design: Carotid artery were removed from wild-type (WT) and RBP7 knockout (KO) mice and treated with either Rosliglitazone (ROSI, 10 uM) or vehicle DMSO (CONT) for 24 hrs.
Retinol-binding protein 7 is an endothelium-specific PPAR<b>γ</b> cofactor mediating an antioxidant response through adiponectin.
Sex, Specimen part, Treatment, Subject
View SamplesDOT1L as methyltransferase of H3K79 is implicated in brian development. Here, we further defined DOT1L function in gene expression during cerebellar development using Microarrays. For that we generated Dot1l knockout mice using a Atoh-Cre driver line resulting in a Dot1l knockout within the cerebellum. The RNA of cerebellar tissue of the Dot1l knockout animals was thereby compared to controls. Additionally we compared the RNA levels of cultured CGNP and CGN samples treated with a DOT1L inhibitor versus DMSO treated cells. The data sets reveals potential new gene expression targets of DOT1L in vivo and in vitro, which ensure a correct development of the cerebellum.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View Samples