We performed single-cell RNA sequencing (RNA-seq) during the in vitro transition of mouse ESCs (mESCs) from a naïve pluripotent state into epiblast-like cells (EpiLCs), a primed pluripotent state. We derived pseudotime expression trajectories to investigate transcript dynamics of key metabolic regulators, with the aim to identify metabolic pathways that potentially impact on early embryonic cell state transitions. Overall design: Single-cell RNA-seq during the in vitro differentiation of mouse embryonic stem cells (ESCs) in 2i culture conditions (time point t=0h) into epiblast-like cells (EpiLCs) at time points t=24h and t=48h.
Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate.
Specimen part, Cell line, Subject
View SamplesHistone deacetylase 1 (HDAC1) is an enzyme that promotes deacetylation of acetylated lysine residues in histones and other proteins. Histone acetylation is often associated with gene activation and expression. Los of HDAC1 leads to severe problems in development and proliferation. Moreover, it seems to be the major histone deacetylase in mouse embryonic stem cells.
Negative and positive regulation of gene expression by mouse histone deacetylase 1.
No sample metadata fields
View SamplesGenotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST Gene Chips. In this dataset we include expression data obtained from 8 normal adrenal medulla and 45 PHEOs/PGLs patient samples.
Genotype and tumor locus determine expression profile of pseudohypoxic pheochromocytomas and paragangliomas.
Sex, Specimen part
View SamplesThe comparison of trancriptomes was part of the study by Pfender, Kuznetsov, Pasternak et al, titled: "Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes". The goal was to check if the oocytes cultured in vitro in follicles (for RNAi studies) correspond to real gametes obtained directly from mice (in vivo). Apart from functional experiments showing that they can be fertilized and develop into an embryo, we also compared transcriptomes of those oocytes. Overall design: 3 samples of 50 oocytes were collected for both groups of in vitro and in vivo grown oocytes.
Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes.
No sample metadata fields
View SamplesPheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors.
A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.
Specimen part
View SamplesComparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls.
Stress-response pathways are altered in the hippocampus of chronic alcoholics.
Sex, Age, Specimen part
View SamplesUsing mice with targeted gene mutations, we identify (1) distinct roles for different canonical Wnt signaling components in central nervous system (CNS) vascular development and in the specification of the blood-brain and blood-retina barriers (BBB and BRB) and (2) differential sensitivities of the vasculature in various CNS regions to perturbations in canonical Wnt signaling components. We find nearly equivalent roles for Lrp5 and Lrp6 in brain vascular development and barrier maintenance but a dominant role for Lrp5 in the retinal vasculature, an especially high sensitivity of the BBB in the cerebellum and pons/interpeduncular nuclei to decrements in canonical Wnt signaling, and plasticity in the barrier properties of mature CNS vasculature. Brain and retinal vascular defects caused by loss of Norrin/Frizzled4 signaling can be fully rescued by stabilizing beta-catenin, and loss of beta-catenin’s transcriptional activation domain or expression of a dominant negative Tcf4 recapitulates the vascular development and barrier defects seen with loss of receptor, co-receptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly by beta-catenin-dependent transcriptional regulation. This work strongly supports a model in which identical or nearly identical canonical Wnt signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB. Overall design: Total retina RNA from P10 WT, NdpKO, Ctnnb1flex3/+;Pdgfb-CreER, and NdpKO;Ctnnb1flex3/+;Pdgfb-CreER mice was subjected to RNAseq
Canonical WNT signaling components in vascular development and barrier formation.
No sample metadata fields
View SamplesOBJECTIVES: Kidney stone diseases are common in premature infants, but the underlying molecular and cellular mechanisms are not fully defined. We carried out a prospective observational study using microarray analysis to identify factors that may be crucial for the initiation and progression of stone-induced injury in the developing mouse kidney.
2,8-dihydroxyadenine nephrolithiasis induces developmental stage-specific alterations in gene expression in mouse kidney.
Sex, Specimen part
View SamplesCompared gene expression in lymphoblasoid cell lines from alcholics and controls and 24 hr treatment with ethanol.
Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression.
Sex, Disease stage, Cell line
View SamplesThe aim of this study was to establish an in vitro model to investigate the initial stages of human implantation based on co-culture of a) immortalized cells representing the receptive (Ishikawa) or non-receptive (HEC-1-A) endometrial epithelium with b) spheroids of a trophoblastic cell line (JEG-3) modified to express green fluorescent protein. After co-culturing Ishikawa cells with trophoblast spheroids, 310 and 298 genes increased or decreased their expression compared to non-co-cultured Ishikawa control cells, respectively; only 9 genes (5 increased and 4 decreased) were differentially expressed in HEC-1-A upon co-culture with trophoblast spheroids. Compared to HEC-1-A, the trophoblast challenge to Ishikawa cells differentially regulated the expression of 495 genes. In summary, upon co-culture with the trophoblast spheroids, non-receptive epithelium is characterized by a muted transcriptional response which in turn fails to activate the full transcriptional response that trophoblast spheroids undergo when co-cultured with receptive epithelium. Overall design: GFP expressing JEG-3 spheroids were co-cultured with confluent monolayers of receptive Ishikawa or non-receptive HEC-1-A epithelia. After 48 hours of co-culture, GFP+ (trophoblast JEG-3 spheroid cells) and GFP- cell fractions (receptive Ishikawa or non-receptive HEC-1-A epithelial cells) were isolated by fluorescence-activated flow cytometry (FACS). The specific transcriptional changes of the isolated cell populations were analyzed by RNA-seq profiling. Statistical significance of gene expression differences was set at an absolute log2 fold change (log2FC) =1 and an adjusted p-value <0.05.
Transcriptomic analysis of the interaction of choriocarcinoma spheroids with receptive vs. non-receptive endometrial epithelium cell lines: an in vitro model for human implantation.
Specimen part, Subject
View Samples