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GSE34000
Rattus norvegicus
9 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
FK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
Publication Title
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
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
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There is a gradient of -catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized -catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of -catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by -catenin activation exhibit activation of Notch signaling and the treatment of -catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.
Publication Title
Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mouse embryonic stem cells (mESCs) fluctuate between a nave inner cell mass (ICM)-like state and a primed epiblast-like state of pluripotency in serum, but are harnessed exclusively in a distinctive, apparently more nave state of pluripotency (the ground state) with inhibitors for mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i). Understanding the mechanism ensuring a nave state of pluripotency would be critical in realizing a full potential of ESCs. We show here that PRDM14, a PR domain-containing transcriptional regulator, ensures a nave pluripotency by a dual mechanism: Antagonizing fibroblast growth factor receptor (FGFR) signaling that is activated paradoxically by the core transcriptional circuitry for pluripotency and directs a primed state and repressing de novo DNA methyltransferases that create a primed epiblast-like epigenome. PRDM14 exerts these functions by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.
Publication Title
PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Patients who cleared HCV viremia early during therapy tended to show favorable outcomes, whereas patients who needed a longer period to clear HCV had poorer outcomes. We explored the mechanisms of treatment resistance by comparing hepatic gene expression before and during treatment
Publication Title
Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.
Publication Title
Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect of the genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc Min/+ mouse model, in which the loss of the Apc gene plays a critical role in tumor development, and established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in the RTCs that were affected by the Apc mutations did not overlap with the genes that were affected in the intestine or those that were affected by the accumulation of beta-catenin in PSCs. The RTCs lacked pluripotency but exhibited the increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. The genetic rescue of the mutated Apc allele conferred pluripotency on the RTCs and enabled their differentiation into various cell types in vivo. The re-disruption of Apc in the RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, yet the majority of intestinal lesions remained pre-tumoral microadenomas. These results highlight the significant influence of the cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on colon tumor promotion.
Publication Title
Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina HiSeq 2000
Description
To dissect regulatory processes of cell proliferation and differentiation we generated mouse strains carrying any combination of the four Stat5 alleles, thus expressing STAT5 from 0 to 100%. RNA-Seq analyses revealed that different STAT5 levels activate specific genetic programs linked to cell proliferation and differentiation. Overall design: We refer to wild-type mice and Stat5abfl/fl mice as AABB mice; Stat5abfl/fl;MMTV-Cre (with Stat5ab-deficient mammary epithelial cells) as Null mice; Stat5a-/- mice as BB mice; Stat5b-/- mice as AA mice; Stat5ab+/null mice as AB mice.
Publication Title
Sequential activation of genetic programs in mouse mammary epithelium during pregnancy depends on STAT5A/B concentration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Splicing profiles in pluripotent stem cells are different from those in somatic cells. Generally, alternative splicing is regulated by RNA binding proteins. To identify the candidate RNA-binding protein-encoding genes, we performed gene expression profiling experiments.
Publication Title
Global splicing pattern reversion during somatic cell reprogramming.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify the genes whose expression levels are changed before and after somatic cell reprogramming, we performed global gene expression analysis of iPS cells and their original fibrobrasts.
Publication Title
Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples