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SRP141163
Mus musculus
3 Downloadable Samples
Illumina Genome Analyzer IIx
Description
A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials. Overall design: Flash frozen NDL(UCD) cell line tumor transplants were sampled and whole-transcriptome analysis was performed by next-generation sequencing (NGS)-based RNA-Sequencing. This series includes three biological replicates of the same cell line grown in three different (but same strain) mouse.
Publication Title
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2500
Description
PHF8 exerts distinct functions in different types of cancer. However, the mechanisms underlying its specific functions in each case remain obscure. To establish whether overexpression of PHF8 regulates the TGF-ß induced the epithelial-mesenchymal transition (EMT), we treated MCF10A-Mock (control) and MCF10A-PHF8wt (overexpressing wild-type PHF8) cells with TGF-ß1 for 0, 24, 48 and 72 hours and performed RNA-seq in biological duplicates. Our data indicated that EMT gene signatures were significantly enriched in MCF10A-PHF8 cells with TGF-ß1 treatment at all time points, strongly indicating that PHF8 overexpression induces a sustained EMT signaling program. Overall design: mRNA profiles of MCF10A-Mock (control) and MCF10A-PHF8 with TGF-ß1 treatment for 0, 24, 48 and 72 hours were generated by RNA-seq, in duplicate, using HiSeq2500 instrument.
Publication Title
Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq1500
Description
Purpose: We have succeeded in the generation and long-term expansion of SOX9-expressing CD271+PDGFRa+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1-CD271hiPDGFRaloCD73- neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/TGFb inhibitor (SB) and FGF2 (hereafter called FSB). When “primed” with TGFb, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. Under the FSB condition, ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages, maintained normal karyotype for at least 10 passages, which any conditions deviated from it (e.g. FGF2 alone or SB alone) failed to support. In order to address the molecular basis of such effects of FSB, a series of RNA-seq experiments were carried out. Methods: We generated and compared the transcriptome profiles of human ectomesenchymal cells expanded under FSB with those cultured under FSB first then under FGF2 alone (F). As a control, we also generated transcriptome of ectomesenchymal cells expanded from the begining under F conditions. RNA-sequencing libraries were prepared using a SureSelect Strand Specific RNA Library Preparation kit (Agilent technologies, Santa Clara, CA). Sequencing was performed on an Illumina HiSeq 1500 using a TruSeq Rapid SBS kit (Illumina, San Diego, CA) in a 50-base single-end mode. Sequenced reads were mapped against the human reference genome (GRCh37), using TopHat v2.0.12 (http://ccb.jhu.edu/software/tophat/index.shtml). Expression levels were calculated as fragments per kilobase of exon per million mapped fragments (FPKMs) using Cufflinks v2.1.1 (http://cole-trapnell-lab.github.io/cufflinks). Results: Ectomesenchymal cells maintained under FSB conditions preferentially expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B, MYCN), cranial mesenchymes (ALX1/3/4) and chondroprogenitors (SOX9, COL2a1) of the neural crest origin (SOX8/9, NGFR, NES). In contrast, those cultured under FSB then F, still expressed SOX4/11/12, but lost LIN28, MYCN, ALX1/3/4, NGFR, COL2a1 expression. Interestingl it enhances expresion ofTGFß-inducible genes such as THBS1/2 and DCN and osteogenesis-related genes such as COL1a1/2 and RUNX1/2. Conclusions: The CD271+CD73+ ectomesenchymal cells accumulated under FSB conditions possess an mRNA profile of proliferating primitive neural crest/ectomesenchymal cells, although they lacked SOX10 expression, which is critical for neural and melanocytic lineage commitment. Transition from FSB to F conditions supressed the proliferation-related genes expression and enhanced the ossification/mineralization, vasculogenesis/angiogenesis, and cardiac myogenesis-related gene expression. Thus, suppression of TGFß signaling by SB does not seem to freeze the developmental stage of the hPSC-derived neural crest during expansion. Such suppression may instead simply support the high proliferative potential of the cells as well as the expression of SOX9 (and COL2a1), and thereby maintain chondrogenic activity. SOX9 expression initiated at the specification and pre-migratory stages is transient in trunk neural crest but persists in cranial neural crest. The chondrogenic CD271+CD73+ ectomesenchymal cells that maintain SOX9 transcription and translation may therefore represent proliferating cranial neural crest, with a slight commitment to non-neural lineages. Overall design: Examination of human ES-derived neural crest-like progenies expanded in 3 different culture media. Each group contains three biological replicates.
Publication Title
Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Total RNA from trichomes of fifth and sixth rosette leaves of three-week-old wild-type and gtl1-1 mutants (Figure 3B) were extracted. We found a total number of 1,759 genes, corresponding to 1,694 probes on the ATH1 chip, that show differential expression of at least 1.3-fold. Out of these 1,694 genes, 47.2% are positively regulated and 52.8% are negatively regulated by GTL1.
Publication Title
Transcriptional repression of the APC/C activator CCS52A1 promotes active termination of cell growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Telogen (resting phase) hair follicles are more radioresistant than anagen (growth phase) ones. Irradiation of BALB/c mice in the anagen phase with -rays at 6 Gy induced hair follicle dystrophy, whereas irradiation in the telogen phase induced the arrest of hair follicle elongation without any dystrophy after post-irradiation depilation. In contrast, FGF18 was highly expressed in the telogen hair follicles to maintain the telogen phase and also the quiescence of hair follicle stem cells. Therefore, the inhibition of FGF receptor signaling at telogen induced the dystrophy after post-irradiation depilation. In addition, the administration of recombinant FGF18 suppressed cell proliferation in the hair follicles and enhanced the repair of radiation-induced DNA damage, so FGF18 protected the anagen hair follicles against radiation damage to enhance hair regeneration. Moreover, FGF18 reduced the expression of cyclin B1 and cdc2 in the skin and FGF18 signaling induced G2/M arrest in the keratinocyte cell line HaCaT, although no obvious change of the expression of DNA repair genes was detected by DNA microarray analysis. These findings suggest that FGF18 signaling for the hair cycle resting phase causes radioresistance in telogen hair follicles by arresting the proliferation of hair follicle cells.
Publication Title
FGF18 signaling in the hair cycle resting phase determines radioresistance of hair follicles by arresting hair cycling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome analysis of LSD2-depleted HepG2 cells revealed that many of the target genes were related to lipid metabolism. We found that LSD2 is an important epigenetic regulator of hepatic lipid metabolism.
Publication Title
Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
In order to investigate the function of heme in the regulation of gene expression, we herein examined variations in mRNA levels in ALA-treated cells from control conditions. A comprehensive anal- ysis by RNA sequencing showed marked changes in the expression of various genes. Among the different amounts of mRNA, we identified the novel heme-inducible protein, SRRD. The plant ho- mologue Sensitivity to Red Light Reduced (SRR1) was previously reported to be involved in the regulation of the circadian clock and phytochrome B signaling in Arabidopsis thaliana. We found that SRRD regulated not only heme biosynthesis, but also the expression of clock genes. The involvement of SRRD in the prolif- eration of cells was also demonstrated. Overall design: Examination of ALA-treated versus untreated NIH3T3 cells.
Publication Title
The novel heme-dependent inducible protein, SRRD regulates heme biosynthesis and circadian rhythms.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Global DNA hypomethylation and DNA hypermethylation of promoter regionsincluding tumor suppressor genesare frequently detected in human cancers. Although many studies have suggested a contribution to carcinogenesis, it is still unclear whether the aberrant DNA hypomethylation observed in tumors is a consequence or a cause of cancer. We found that overexpression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA hypomethylation and transformation in NIH3T3 cells. This hypomethylation was due to the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent impairment of Dnmt1 localization. In addition, enforced expression of Stella enhanced the metastatic ability of B16 melanoma cells through the induction of metastasis-related genes by inducing DNA hypomethylation of their promoter regions. Such DNA hypomethylation itself causes cellular transformation and metastatic ability. These data provide new insight into the function of global DNA hypomethylation in carcinogenesis.
Publication Title
Global DNA hypomethylation coupled to cellular transformation and metastatic ability.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure.
Sample Metadata Fields
Specimen part
View Samples