We used transcription-profiling to identify mitogen-activated protein kinase (Mapk) signaling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signaling by elevation of intracellular levels of cAMP using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolyzing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination.
Retinoid X receptor gamma signaling accelerates CNS remyelination.
Specimen part
View SamplesRNA sequencing was performed to investigate ionizing radiation-dependent transcriptional change in human pluripotent cells and differentiated cells. Overall design: Examined 3 types of cells (fibroblasts, iPS cells and neural progenitor cells) and 2 types of treatments (non IR or IR), total 6 samples were analyzed.
Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.
Specimen part, Treatment, Subject
View SamplesGenome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.
Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice.
Sex, Specimen part
View SamplesIn the present study, we investigated the effect of CBM 588 on lifespan and multiple-stress resistance using Caenorhabditis elegans as a model animal. When adult C. elegans were fed a standard diet of Escherichia coli OP50 or CBM 588, the lifespan of the animals fed CBM 588 was significantly longer than that of animals fed OP50. Moreover, the worms fed CBM 588 were more resistant to certain stressors, including infections with pathogenic bacteria, UV irradiation, and the metal stressor Cu2+. CBM 588 failed to extend the lifespan of the daf-2/IR, daf-16/FOXO and skn-1/Nrf2 mutants. Transcriptional profiling comparing CBM 588-fed and control-fed animals suggested that DAF-16-dependent class II genes were regulated by CBM 588. In conclusion, CBM 588 extends the lifespan of C. elegans probably through regulation of the insulin/IGF-1 signaling (IIS) pathway and the Nrf2 transcription factor, and CBM 588 improves resistance to several stressors in C. elegans. Overall design: Transcriptional profiling of eight-day-old worms that were fed OP50 or CBM 588 for five days, by deep sequencing, using Illumina HiSeq.
<i>Clostridium butyricum</i> MIYAIRI 588 Increases the Lifespan and Multiple-Stress Resistance of <i>Caenorhabditis elegans</i>.
Sex, Cell line, Treatment, Subject
View SamplesThe forced expression of Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc) reprograms cells into induced pluripotent stem cells (iPSCs) through a series of sequential cell fate conversions. The order and robustness of gene expression changes are highly depended on the Yamanaka factor stoichiometry. We specifically focused on two different reprogramming paths induced by high- and low-Klf4 stoichiometry, which were accomplished by introducing OK+9MS or OKMS polycistronic cassettes, respectively, into mouse embryonic fibroblasts. By comparing these reprograming intermediates with embryonic stem cells (ESCs) and primary keratinocytes, we identified high-Klf4 specific, transiently up-regulated epithelial genes. We found that expression of these epithelial genes was enriched in a TROP2-positive cell population. Moreover, we identified a set of transcription factors which are candidates for the regulation of transiently expressed epithelial genes, and revealed their connection to high-Klf4-specific reprogramming hallmarks.
OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates.
Specimen part, Treatment
View SamplesZinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon.
Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain.
Specimen part
View SamplesWe identify perhexiline, a small molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1 induced leukemias in vitro and in vivo. Overall design: RNA-Seq from CUTLL1 cell lines treated with Perhexiline or vehicle for 3 days
Therapeutic targeting of HES1 transcriptional programs in T-ALL.
No sample metadata fields
View SamplesCD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).
Specimen part
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
The Msx1 Homeoprotein Recruits Polycomb to the Nuclear Periphery during Development.
Specimen part, Cell line
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