In mammals, chromosomes are partitioned into megabase-sized topologically associating domains (TADs). TADs can be in either A (active) or B (inactive) subnuclear compartments, which correspond to early (E) and late (L) replicating timing (RT) domains, respectively. Here, we show that RT changes are tightly correlated with A/B compartment changes during mouse embryonic stem cell (mESC) differentiation. A/B compartments changed mostly by a “boundary shift,” frequently causing compartment switching of single TADs, which coincided with or preceded RT changes. Upon differentiation, mESCs acquired an A/B compartment organization that closely resembled EpiSCs (epiblast-derived stem cells), suggesting that accumulation of compartment boundary repositioning eventually led to naïve-to-primed pluripotency transition in A/B compartment organization. We propose that large-scale reorganization of A/B compartments, which is reflected in RT domain reorganization, represents major cell fate changes. Collectively, our data provides valuable insights into the regulatory principles of 3-dimensional (3D) genome organization during early embryonic stages. Overall design: RNA-Seq: 9 cell types, with a total of 34 individual replicates.
Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization.
Specimen part, Subject
View SamplesExpression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.
Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.
Specimen part, Treatment
View SamplesIdentifying novel candidate biomarker gene differentially expressed in the peripheral blood cells of patients with early stage acute myocardial infarction using microarray as a high throughput screening technology.
Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome.
Specimen part, Disease, Time
View SamplesThe fetal ovarian grafts under the kidney capsule of adult male mice undergo a partial sex-reversal showing ectopic SOX9-positive Sertoli cell-like cells around 15-20 days post-transplantation. However, the molecular bases of such masculinization of fetal ovaries in the paternal environment were unclear.
Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice.
Specimen part
View SamplesStudy of the Arabidopsis circadian clock.
A hierarchical multi-oscillator network orchestrates the Arabidopsis circadian system.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Specimen part
View SamplesMulticellular organisms consist of multiple cell types, whose identities are maintained appropriately at locations where they are reside. The identity of each cell type is primarily maintained by cell-type-specific gene expression programs, but mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease -actin monomer resulted in nuclear accumulation of Mkl1 and the activation of Srf, which downregulated cell-type-specific genes and altered epigenetics in enhancers and chromatin organization. Mice overexpressing Srf exhibited various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Specimen part
View SamplesWe used an Aldefluor assay system to study the signaling pathways that regulate the frequency and maintenance of ALDH-positive cell population in MCF-7 cells as a CSC model.
Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation.
Cell line
View SamplesComparison of gene expression profile between an 96 day human retina and photoreceptors present around the same time.
Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells.
Specimen part
View SamplesAddition of CO2 to the inspired gas can ameliorate lung injury during high tidal volume mechanical ventilation in animal models. Although some effects of hypercapnia on physiology and cell signaling have been characterized, we hypothesized that assessment of genome-wide gene expression patterns would reveal novel pathways of protection.
α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury.
Sex, Specimen part
View Samples