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GSE39064
Mus musculus
2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Roles of mesothelial cells (MCs) are poorly understood during liver development and injury. We identified podoplanin (Pdpn) as a cell surface markers for mesothelial cells in E12.5 mouse developing liver.
Publication Title
Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There are a few markers for embryonic hepatic stellate cells in mouse embryonic livers
Publication Title
Isolation of a unique hepatic stellate cell population expressing integrin α8 from embryonic mouse livers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There are a few markers available to distinguish hepatic stellate cells (HSCs), portal fibroblasts (PFs), and mesothelial cells (MCs) in the adult mouse liver.
Publication Title
Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Genetically engineered mouse models of lung cancer have demonstrated an important role in understanding the function of novel lung cancer oncogenes and tumor suppressor genes identified in genomic studies of human lung cancer. Further, these models are important platforms for pre-clinical therapeutic studies. Here, we generated a mouse model of lung adenocarcinoma driven by mutation of the Discoidin Domain Receptor 2 (DDR2) gene combined with loss of TP53. DDR2L63V;TP53L/L mice developed poorly differentiated lung adenocarcinomas in all transgenic animals analyzed with a latency of 40-50 weeks and a median survival of 67.5 weeks. Mice expressing wild-type DDR2 with combined TP53 loss did not form lung cancers. DDR2L63V; TP53L/L tumors displayed robust expression of DDR2 and immunohistochemical markers of lung adenocarcinoma comparable to previously generated models of lung adenocarcinoma though also displayed concomitant expression of the squamous cell markers p63 and SOX2. Tumor-derived cell lines were not solely DDR2 dependent and displayed up-regulation of and partial dependence on MYCN. Combined treatment with the BET inhibitor JQ1 and the mutltitargeted DDR2 inhibitor dasatinib inhibited tumor growth in vitro and in vivo. Together, these results suggest that DDR2 mutation can drive lung cancer initiation in vivo and provide a novel mouse model for lung cancer therapeutics studies.
Publication Title
NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination Therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
NextSeq 500
Description
To establish effective multitargeted KRAS pathway therapy, we analyzed mediators of acquired resistance to chronic momelotinib and MEK inhibitor exposure in A549 cells. Since inhibitor resistance was completely reversible after drug withdrawal for several passages, suggesting epigenetic reprogramming, we investigated whole mRNA expression profiles in A549, momelotinib and selumetinib resistant (MSR)-A549 cells and MSR-A549 cells following drug withdrawal for 10 days. In parallel, we also examined mRNA expression profiles of MSR-A549 cells treated with the BET inhibitor JQ1, to identify specific targets regulated by H3K27 acetylation. Overall design: mRNA profile of MSR-A549 cells with or without JQ1 treatment.
Publication Title
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We generated h-hepatocyte chimeric mice with livers that were predominantly repopulated with h-hepatocytes in a h-growth hormone (GH)-deficient state. Using microarray profiles, comparison between h-hepatocytes from h-GH-treated and untreated mice identified 14 GH-up-regulated and four GH-down-regulated genes, including IGF-1, SOCS2, NNMT, IGFLS, P4AH1, SLC16A1, and SRD5A1, and FADS1 and AKR1B10, respectively.
Publication Title
Growth hormone-dependent pathogenesis of human hepatic steatosis in a novel mouse model bearing a human hepatocyte-repopulated liver.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The molecular chaperons FK506-binding proteins (Fkbps) comprise one of three families of peptidyl prolyl isomerases, which promote the transition between cis- and trans-conformations of peptidyl prolyl bonds. Mouse Fkbp family is composed of at least 15 members, but the functions of the large family in cell proliferation and differentiation remain elusive. During myoblast differentiation, the cells need to exit the cell cycle before fusion and terminal differentiation to form myotubes. The clear distinction between proliferation and differentiation provides an ideal model with which to investigate the roles of Fkbps in these two cell biological events. We found that depletion of FkbpC in mouse myoblasts delayed the exit from the cell cycle and expression of myotube-specific genes, whereas its overexpression caused opposite effects. At a mechanistic level, our study revealed a crucial function of FkbpC in Cdk4 activation during myoblast proliferation. Cdk4 undergoes conformational changes in the HSP90/Cdc37/Cdk4 complex as a prerequisite for activation through binding to CyclinD1 accompanied by phosphorylation. Our results showed that FkbpC depletion released Cdk4 from the HSP90 complex, which increased the Cdk4/CyclinD1 complex in myoblasts and sustained high levels of phosphorylated Cdk4 and Rb during differentiation. These results explain the delayed cell cycle exit and differentiation in the depleted cells. In addition, after synchronizing the cell cycle of myoblasts we found dynamic changes of the amounts of FkbpC and Cdk4 in the HSP90 complex during the G1/S transition. Knockout mice of FkbpC demonstrated delayed muscle regeneration after chemical damage, providing an in vivo evidence for the essential role of FkbpC in muscle differentiation. Collectively, our study uncovered FkbpC's critical function as a novel switch regulating the transition from proliferation to differentiation through controlling one of the central regulators of proliferation, Cdk4. Overall design: mRNA profiles of Fkbp4 knockdown, Fkbp5 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Publication Title
Promotion of Myoblast Differentiation by Fkbp5 via Cdk4 Isomerization.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DNA methylation has been considered to play an important role during myogenic differentiation. In terminal differentiation of myoblasts, chronological alteration of DNA methylation status was poorly understood. Using Infinium HumanMethylation450 BeadChips, we validated genome wide DNA methylation profiles of human myoblast differentiation models. To investigate correlation between DNA methylation and gene expression, we also assessed gene expression of myoblasts with GeneChip Human Genome U133 Plus 2.0 array.
Publication Title
DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation.
Sample Metadata Fields
Sex, Age, Race
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis for the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function in spermatogenesis has been recently elucidated. Nevertheless, Zfy gene targeting analysis has not been performed thus far. Here, we adopted the highly efficient CRISPR/Cas9 system to generate individual Zfy1 or Zfy2 knockout (KO) mice, and Zfy1 and Zfy2 double knockout (Zfy1/2-DKO) mice. While individual Zfy1 or Zfy2-KO mice did not show any significant phenotypic alterations in fertility, Zfy1/2-DKO mice were infertile and displayed abnormal sperm morphology, fertilization failure, and early embryonic development failure. Mass spectrometric screening, followed by confirmation with western blot analysis, showed that PLCZ1, PLCD4, PRSS21, and HTT protein expression was significantly deceased in spermatozoa from Zfy1/2-DKO mice compared with those from wild type mice. These results are consistent with the phenotypic changes seen in the double mutant mice. Collectively, our strategy and findings revealed that Zfy1 and Zfy2 have redundant functions in spermatogenesis, facilitating a better understanding of fertilization failure and early embryonic development failure.
Publication Title
Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking Cry2 display premature cell cycle exit and form short myotubes due to inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2-/- mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell cycle exit and inefficient cell fusion. This study uncovers a post-transcriptional regulation of myogenic differentiation by circadian rhythms. Overall design: mRNA profiles of Cry1 knockdown, Cry2 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Publication Title
Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples