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GSE46532
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, while it is required and even stimulating during the late stage. Mechanistically, this biphasic effect of Wnt signaling is accompanied by a change in the requirement of all four of its transcriptional effectors: Tcf1, Lef1, Tcf3, and Tcf4. For example, Tcf3 and Tcf4 are stimulatory early but inhibitory late in the reprogramming process. Accordingly, ectopic expression of Tcf3 early in reprogramming combined with its loss-of-function late enables efficient reprogramming in the absence of ectopic Sox2. Together, our data indicate that the step-wise process of reprogramming to iPSCs is critically dependent on the stage-specific control and action of all four Tcfs and Wnt signaling.
Publication Title
Stage-specific regulation of reprogramming to induced pluripotent stem cells by Wnt signaling and T cell factor proteins.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Detailed analysis comparing hiPSC lines that were newly generated and compared them to already established hiPSC lines
Publication Title
Molecular analyses of human induced pluripotent stem cells and embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Contractile and highly synthetic myofibroblasts are the key effector cells involved in excessive extracellular matrix (ECM) deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). In order to define the key drivers of the fibrotic response, we used laser capture microdissection to isolate RNA from myofibroblasts within fibroblastic foci and performed microarray analysis in combination with a novel eigengene approach to identify functional clusters of genes which associate with collagen gene expression.
Publication Title
Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Numerous studies have shown the potential of spermatozoal RNAs to delineate failures of spermatogenic pathways in infertile samples. However, the RNA contribution of normal fertile samples still needs to be established in relation to transcripts consistently present in human spermatozoa. We report here the spermatozoal transcript profiles characteristic of 24 normally fertile individuals. RNA was extracted from the purified sperm cells of ejaculate and hybridized to Illumina Human-8 BeadChip Microarrays
Publication Title
Identification of human sperm transcripts as candidate markers of male fertility.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Human fibroblasts at different population doublings were treated with low amounts of rotenone (mild stress) and compared to untreated fibroblasts. Two different cell lines were used (MRC-5, HFF). Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 60 samples: 3 biological replicates for each group: MRC-5 cells at 4 different population doublings (PD) with and without rotenone; HFF cells at 6 different population doublings with and without rotenone
Publication Title
Hormetic effect of rotenone in primary human fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
There is emerging evidence that, beyond their cholesterol lowering properties, statins exhibit important antileukemic effects in vitro and in vivo, but the precise mechanisms by which they generate such responses remain to be determined. We have previously shown that statins promote differentiation of acute promyelocytic leukemia (APL) cells and enhance generation of all-trans-retinoic acid (ATRA)-dependent antileukemic responses. We now provide evidence that statin-dependent leukemic cell differentiation requires engagement and activation of the JNK kinase pathway. In addition, in experiments to define the molecular targets and mediators of statin-induced differentiation we found a remarkable effect of statins on ATRA-dependent gene transcription, evidenced by the selective induction of over 400 genes by the combination of atorvastatin and ATRA. Altogether, our studies identify novel statin molecular targets linked to differentiation, establish that statins modulate ATRA-dependent transcription, and suggest that combined use of statins with retinoids may provide a novel approach to enhance antileukemic responses in APL and possibly other leukemias.
Publication Title
Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate, and 3-deazaneplanocin A (DZNep). In order to determine how B+D affects global gene expression, we performed microarray analysis in triplicate in the HSF-6 (8) C and HSF-6 (8) B+D treated cultures. We also evaluated HSF-6 (S9) B+D in triplicate and identified no statistically significant changes in gene expression in HSF-6 (S9) B+D compared to HSF-6 (8) B+D treated cultures. This suggests that global transcriptional differences are more strongly modulated by presence or absence of B+D and not the percentage of class I, II or III nuclei.
Publication Title
Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Induced pluripotent stem (iPS) cells can be obtained from fibroblasts by expression of Oct4, Sox2, Klf4, and c-Myc. To determine how these factors induce this change in cell identity, we carried out genomewide promoter analysis of their binding in iPS and partially reprogrammed cells. Most targets in iPS cells are shared with ES cells and the factors cooperate to activate the ES-like expression program. In partially reprogrammed cells, genes bound by c-Myc have achieved a more ES-like binding and expression pattern. In contrast, genes that are co-bound by Oct4, Sox2, and Klf4 in ES cells and that encode pluripotency regulators show severe lack of both binding and transcriptional activation. Among the factors, c-Myc has a pivotal effect on the initiation of the ES transcription program, including the repression of fibroblast-specific genes. Our analysis begins to unravel how the four factors function together and suggests a temporal and separable order of their effects during reprogramming.
Publication Title
Role of the murine reprogramming factors in the induction of pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Nearly all colorectal cancers have dysregulated Wnt signalling, predominantly through the mutation of the Apc (Adenomatous Polyposis Coli) gene. Therefore it is of vital importance to elucidate the key Wnt target genes in intestinal cells in vivo. We have used a novel inducible cre-lox based murine system (designated ApcFlox) to investigate the consequences of perturbation of Wnt signalling following inactivation of Apc in vivo within 100% of the intestinal epithelium. We have employed microarray analysis at 3 time points within our ApcFlox system (Day 3 prior to the onset of phenotype, day 4 the establishment of the phenotype and day 5 gross phenotype of altered proliferation, differentiation and migration) and from adenomas arising in the ApcMin/+ background allowing us characterise Wnt/beta-catenin target genes based on their expression profiles during different stages of intestinal tumourigenesis. Furthermore, we have employed microarray analysis using livers from our ApcFlox system and have demonstrated that there is very little overlap in the Wnt target genes induced by Apc loss in the liver and the intestine. More importantly, we have been able to determine a novel set of putative Wnt/beta-catenin target genes which are upregulated at both early and late stages of tumourigenesis in the intestine and may represent novel therapeutic targets in colon cancer.
Publication Title
Hunk/Mak-v is a negative regulator of intestinal cell proliferation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina Genome Analyzer
Description
Oct4, Sox2, Klf4, and cMyc (OSKM) reprogram somatic cells to pluripotency. To gain a mechanistic understanding of their function, we mapped OSKM-binding, stage-specific transcription-factors (TFs), and chromatin-states in discrete reprogramming stages and performed loss- and gain-of-function experiments. We found that early in reprogramming OSK extensively bind somatic-enhancers and initiate their decommissioning by recruiting Hdac1. Concurrently, OSK engage other sites, including specific pluripotency-enhancers, and induce the relocation of somatic TFs to these sites and away from somatic-enhancers, extending somatic-enhancer decommissioning genome-wide. Pluripotency-enhancer selection early in reprogramming occurs predominantly at sites with high OSK-motif densities and requires collaborative binding by OSK. Most pluripotency-enhancers are selected later and occupied by OS and stage-specific-TFs like Esrrb. Overexpression of stage-specific-TFs influences reprogramming efficiency by changing OSK-occupancy, somatic-enhancer decommissioning, and pluripotency-enhancer selection. We propose that collaborative interactions among OSK and with stage-specific-TFs direct both somatic-enhancer decommissioning and pluripotency-enhancer selection, which drives the enhancer reorganization underlying reprogramming Overall design: RNA-seq
Publication Title
Cooperative Binding of Transcription Factors Orchestrates Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples