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GSE116309
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The 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.
Publication Title
OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Oct3/4, Sox2, Klf4, and c-Myc re-wire somatic cells to achieve induced pluripotency (iPS cells). However, subtle differences in reprogramming methodology may confound comparative studies of reprogramming-induced gene expression changes. We specifically focused on the design of polycistronic reprogramming constructs, which encode all four factors linked with 2A peptides. Notably, publically available cassettes were found to employ one of two Klf4 variants (Klf4S and Klf4L; GenBank Accession Nos: AAC52939.1 and AAC04892.1), differing only by nine N-terminal amino acids. In a polycistronic context, these two variants generated dissimilar protein stoichiometry, where Klf4L vectors produced more Klf4 protein than those encoding Klf4S.
Publication Title
KLF4 N-terminal variance modulates induced reprogramming to pluripotency.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The 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.
Publication Title
Protein kinase A accelerates the rate of early stage differentiation of pluripotent stem cells.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
It remains controversial whether human induced pluripotent stem cells (hiPSCs) are distinct from human embryonic stem cells (hESCs) in their molecular signatures and differentiation properties. We examined the gene expression and DNA methylation of 49 hiPSC and 10 hESC lines and identified no molecular signatures that distinguished hiPSCs from hESCs. Comparisons of the in vitro directed neural differentiation of 40 hiPSC and four hESC lines showed that most hiPSC clones were comparable to hESCs. However, in seven hiPSC clones, significant amount of undifferentiated cells persisted even after neural differentiation and resulted in teratoma formation when transplantated into mouse brains. These differentiation-defective hiPSC clones were marked by higher expression of several genes, including those expressed from long terminal repeats of human endogenous retroviruses. These data demonstrated that many hiPSC clones are indistinguishable from hESCs, while some defective hiPSC clones need to be eliminated prior to their application for regenerative medicine.
Publication Title
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 105 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Specification 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.
Publication Title
Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 70 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
Many 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.
Publication Title
Tissue-specific clocks in Arabidopsis show asymmetric coupling.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Induction of mouse germ-cell fate by transcription factors in vitro.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 46 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Spermatogonial 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.
Publication Title
Regulation of pluripotency in male germline stem cells by Dmrt1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
Sample Metadata Fields
Sex, Specimen part, Disease stage, Subject
View Samples