Filters
Technology
Platform
GSE27656
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stable activation of the WNT signaling effector beta-catenin (CTNNB1(ex3) in ovarian granulosa cells results in the formation of premalignant lesions that develop into granulosa cell tumors (GCTs) spontaneously later in life. Loss of the tumor suppressor gene Pten accelerates GCT formation in the CTNNB1 strain. Conversely, expression of oncogenic KRASG12D causes the dramatic arrest of proliferation, differentiation and apoptosis in granulosa cells, and consequently, small abnormal follicle-like structures devoid of oocytes accumulate in the ovary. Because of the potent anti-proliferative effects of KRASG12D in granulosa cells, we sought to determine if KRASG12D would block precancerous lesion and tumor formation in follicles of the CTNNB1 mutant mice. Unexpectedly, transgenic Ctnnb1;Kras mutant mice developed early-onset GCTs leading to premature death in a manner similar to theCtnnb1;Pten mutant mice. Moreover, the GCTs in the Ctnnb1;Kras mutant mice exhibited increased GC proliferation, decreased apoptosis and impaired differentiation. Microarray and RT-PCR analyses revealed that ovaries from mice expressing dominant-stable CTNNB1 with either Pten loss or KRAS activation were unpredictably similar. Specifically, gene regulatory processes induced by CTNNB1 were mostly enhanced by either KRAS activation or Pten loss in remarkably similar patterns and degree. Furthermore, the concomitant activation of CTNNB1 and KRAS in Sertoli cells resulted in the development of granulosa cell tumors of the testis. RT-PCR studies showed a partial overlap in gene regulatory processes associated with tumor development in the ovary and testis. Together, these results suggest that KRAS activation and Pten loss induce GCT development from premalignant lesions via highly similar molecular mechanisms.
Publication Title
Either Kras activation or Pten loss similarly enhance the dominant-stable CTNNB1-induced genetic program to promote granulosa cell tumor development in the ovary and testis.
Sample Metadata Fields
Age, Specimen part
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
GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
Publication Title
GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
Publication Title
GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
Publication Title
GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 151 Downloadable Samples
IlluminaGenomeAnalyzer
Description
To increase our understanding of psoriasis, we utilized RNA-seq to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived cDNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ~38 million single-end 80-bp reads per sample. Comparison of 42 samples* examined by both RNA-seq and microarray [GSE13355] revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes. Weighted gene co-expression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long non-coding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally-expressed genes were significantly down-regulated in psoriatic biopsies, most likely due to expansion of the epidermal compartment. These results demonstrate the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and co-expression analysis. *The list of 42 samples examined by both RNA-seq and microarray is provided in the 'MAoverlappedsamples.txt'. Overall design: 92 psoriatic and 82 normal skin samples
Publication Title
Circadian control of interferon-sensitive gene expression in murine skin.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 45 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Together with the GSE54456 data, we used in total RNA-seq data from 99 lesional psoriatic, 27 uninvolved psoriatic, and 90 normal skin biopsies and applied computational approaches to identify and characterize expressed lncRNAs. Overall design: 7 psoriatic, 27 uninvolved, and 8 normal skin samples
Publication Title
Circadian control of interferon-sensitive gene expression in murine skin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Imiquimod (IMQ) is a topical therapeutic immune activator that causes psoriasiform inflammation in mice. To determine if IMQ-induced inflammation and gene expression changes depended on the time of day in which treatment is administered, we performed gene expression profiling of dorsal mouse back skin by microarray after different durations of topical 1% IMQ treatment (control = no treatment, 6 hr, 24 hr, and 5 days of IMQ treatment) at different times of day (ZT01, ZT07, ZT09 = day-time treatment; ZT13 and ZT19 = night-time treatment). We also performed a time course after IMQ treatment by collecting mouse back skin after 0 (no treatment), 1, 2, 4, 6, and 24 hours post-treatment. Lastly, we determined gene expression changes in response to IMQ in mice deleted for the core circadian clock gene, Bmal1, after 0 (no treatment) and 24 hours post-1% IMQ compared to Wt (both treated and collected during the daytime at ZT09). The results of this study are important as they show that IMQ-induced activation of interferon sensitive genes are diurnal in Wt mice after 6 hours and 24 hours but not after 5 consecutive treatments. Furthermore, we find that interferon sensitive genes are induced more robustly in the skin of Bmal1 KO mice after 24 hr IMQ compared to Wt mice. These results are important for further understanding how the circadian clock regulates immune activation in response to the theraputic agent IMQ.
Publication Title
Circadian control of interferon-sensitive gene expression in murine skin.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 61 Downloadable Samples
- Illumina HiSeq 2000
Description
Panel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines
Publication Title
Interleukin 32 expression in human melanoma.
Sample Metadata Fields
Disease, Disease stage, Cell line, Subject
View Samples- Mus musculus
- 55 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Background: Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. Whether this phenotype depends on strain or sex has never been systematically investigated on a large scale. Such effects, however, could lead to conflicts among studies, while further impacting study outcomes and efforts to translate research findings. Methods: RNA-seq was used to evaluate the psoriasiform phenotype elicited by IMQ in both sexes of 7 mouse strains (C57BL/6J, BALB/cJ, CD1, DBA/1J, FVB/NJ, 129X1/SvJ and MOLF/EiJ). Results: In most strains, IMQ altered gene expression in a manner consistent with human psoriasis, partly due to innate immune activation and decreased homeostatic gene expression. The IMQ response of MOLF males was aberrant, however, with decreased expression of differentiation-associated genes (elevated in other strains). Key aspects of the IMQ response differed between the two most commonly studied strains (BALB/c and C57BL/6). Compared with BALB/c, the C57BL/6 phenotype showed increased expression of genes associated with DNA replication, IL-17A activation and CD8+ T cells, but decreased expression of genes associated with interferon signaling and CD4+ T cells. Surprisingly, although IMQ-induced expression shifts mirrored psoriasis, correspondence was similar or better for other human skin diseases (e.g., eschars, acne, atopic dermatitis). For BALB/c, MOLF, and 129X1 strains, genes altered by IMQ corresponded better to those altered in human skin infections or wounds compared with those altered in psoriasis lesions. Conclusions: These findings demonstrate strain-dependent aspects of IMQ dermatitis that warrant consideration in planning and interpreting experimental studies. We have further shown that IMQ does not uniquely model psoriasis but in fact triggers a core set of pathways active in diverse skin diseases. These observations challenge the view of IMQ dermatitis as a mouse phenotype uniquely appropriate for studying psoriasis as opposed to other human skin conditions. Overall design: RNA-seq was used to investigate the psoriasiform phenotype that develops following topical IMQ treatment in male and female mice of 7 laboratory mouse strains (C57BL/6J, BALB/cJ, CD1, DBA/1J, FVB/NJ, 129X1/SvJ and MOLF/EiJ). Mouse back skin was treated with 62.5 mg AldaraTM (5% IMQ) or a non-toxic lanolin-derived occlusion cream (CTL) once per day for 5 consecutive days. Mice were sacrificed on day 6 and skin biopsies were collected. Overall, RNA-seq was used to profile transcriptomes of 56 CTL- and IMQ-treated skin samples (7 strains × 2 sexes × 2 treatments; n = 2 samples per strain/sex/treatment combination).
Publication Title
Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples