This 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 SamplesThe rate of cell differentiation is tightly controlled and critical for normal development and stem cell differentiation. However, so far it has been difficult to control the rate of ESCs differentiation. Here we report the acceleration of the differentiation rate due to the activation of protein kinase A (PKA) and the associated early loss of embryonic stem cells (ESCs) pluripotency markers and the early appearance of mesodermal and other germ layer cell markers.
Protein kinase A accelerates the rate of early stage differentiation of pluripotent stem cells.
Time
View SamplesSpecification of germ cell fate is fundamental in development. With a highly representative single-cell microarray and rigorous quantitative-PCR analysis, we defined the genome-wide transcription dynamics that create primordial germ cells (PGCs) from the epiblast, a process that exclusively segregates them from their somatic neighbors. We also analyzed the effect of the loss of Blimp1, a key transcriptional regulator, on these dynamics. Our analysis revealed that PGC specification involves complex, yet highly ordered regulation of a large number of genes, proceeding under the strong influence of mesoderm induction with active repression of specific programs such as epithelial-mesenchymal transition, Hox gene activation, cell-cycle progression and DNA methyltransferase machinery. Remarkably, Blimp1 is essential for repressing nearly all the genes normally down-regulated in PGCs relative to their somatic neighbors, whereas it is dispensable for the activation of approximately half of the genes up-regulated in PGCs.
Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice.
No sample metadata fields
View SamplesMany organisms acquired circadian clock system to adapt daily and seasonal environmental changes. Mammals have the master clock in the brains suprachiasmatic nucleus (SCN) that synchronizes other circadian clocks in the peripheral tissues or organs. Plants also have circadian clock in their bodies, but the presence of the tissue-specific functions of circadian clock is remained elusive. The aim of this experiment is to compare tissue-specific gene expression profile using gene expression Microarray.
Tissue-specific clocks in Arabidopsis show asymmetric coupling.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induction of mouse germ-cell fate by transcription factors in vitro.
Sex, Specimen part
View SamplesSpermatogonial stem cells (SSCs) have pluripotent potential. However, frequency of pluripotent cell derivation is low and the mechanism of culture-induced reprogramming remains unknown. Here we report that epigenetic instability of germline stem (GS) cells, cultured SSCs, induces pluripotent cell derivation. GS cells undergo DNA demethylation in H19 differentially methylated region under low-density culture. When H19 demethylation was induced by Dnmt1 depletion, they converted into embryonic stem (ES)-like cells. Dnmt1 depletion downregulated Dmrt1 expression, whose depletion also induced pluripotency. Functional screening of Dmrt1 target gene revealed that Dmrt1 depletion upregulates Sox2, the key molecule responsible for generating induced pluripotent stem cells. Although Sox2 transfection upregulated Oct4 and produced pluripotent cells, this conversion was inhibited by Oct1 overexpression, suggesting that the balance of Oct proteins maintains SSC identity. These results suggest that culture-induced reprogramming is caused by unstable DNA methylation, and that Dmrt1-Sox2 cascade is critical for regulating pluripotency in SSCs.
Regulation of pluripotency in male germline stem cells by Dmrt1.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
Sex, Specimen part, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis.
No sample metadata fields
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