We performed RNAseq analysis to determine the effect of MFN1 deletion on oocyte global gene expression profile. RNAseq revealed a total of 982 genes were significantly differentially expressed (p<0.05) in Mfn1-/- oocytes compared to WT (654 up-regulated and 337 down-regulated). Pathway analysis indicated significant over-representation of elements involved in regulation of ceramide biosynthesis, death receptor signaling and adherens junction signaling. Differential expression of these genes (Bad, G2e3, Cdh17 and Myh2) was also confirmed by qRT-PCR.Our findings provide new insight into the role of MFN1 in the oocytes, and may help understand the potential mechanism of infertility and reproductive aging associated with MFN1-deficiency. Overall design: Secondary follicle-enclosed oocytes were collected from 8-week-old Mfn1-/- and WT mice (n=3 for each group) and 5 oocytes from each group were pooled for RNA sequencing analysis.
Mitofusin 1 is required for female fertility and to maintain ovarian follicular reserve.
Cell line, Subject
View SamplesARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumors. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylated the Lysine 120 residue of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates p53' apoptotic function by upregulating HDAC6. These results indicate that pharmacological inhibition of HDAC6 is a novel therapeutic strategy involving ARID1A-mutation Overall design: RNA-seq transcription profiling of samples with altered HDAC6 activity
ARID1A-mutated ovarian cancers depend on HDAC6 activity.
Specimen part, Cell line, Treatment, Subject
View SamplesIt is possible to identify the key genes and pathways involved in specific physiological processes using transcriptome analyses. However, these powerful new deep sequencing-based methods have rarely been applied to studies of memory function. We used the bow-tie maze to train rats by exposing them to highly familiar objects or to novel objects. Total RNA sequencing was then used to compare the transcriptome of the perirhinal cortices of naïve control rats and rats exposed to novel and familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats and these included genes coding for transcription factors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures. Overall design: RNA profiles of perirhinal cortex from rats exposed to novel objects (n=5) or familiar objects (n=5) in a recognition memory task were investigated using the Ion Proton System. Controls were naïve rats that had not undergone any behavioural testing (n=4).
Recognition memory-induced gene expression in the perirhinal cortex: A transcriptomic analysis.
No sample metadata fields
View SamplesSamples used for hybridization consisted of non-pooled (NP) RNA extracts from 8 groups in each of two time periods after drug administration: oil vehicle treated control embryonic limb bud mesoderm and ectoderm, phosphate buffered saline vehicle control embryonic limb bud mesoderm and ectoderm, acetazolamide treated embryonic limb bud mesoderm and ectoderm, and cadmium sulfate treated embryonic limb bud mesoderm and ectoderm. Forty-eight hybridization experiments were on non-pooled (NP) individual RNA extracts.
Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide.
No sample metadata fields
View SamplesThe goal of this experiment was to examine the innate immune response to helminth infection in the lung. Hookworms (like many other helminths) use an obligate migration pathway through the lung. Their infection has been characterized in the gut in detail, but early immune responses in the lung have not been fully characterized.
Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.
No sample metadata fields
View SamplesProtein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection.
Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency.
Specimen part
View SamplesTo uncover novel molecules involved in taste detection, we performed a microarray-based screen for genes enriched in taste neurons. Proboscis RNA from flies homozygous for a recessive poxn null mutation was compared to RNA from heterozygous controls. Poxn mutants have a transformation of labellar gustatory chemosensory bristles into mechanosensory bristles and therefore lack most or all taste neurons.
The molecular basis for water taste in Drosophila.
Sex
View SamplesMacrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons.
Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.
Specimen part
View SamplesThese data show that the genes that distinguish myofibroblasts from fibroblasts are myriad, and that some genes not traditionally associated with myofibroblast differentiation may serve as novel therapeutic targets for fibrosing disorders.
Reversal of the Transcriptome by Prostaglandin E2 during Myofibroblast Dedifferentiation.
Specimen part, Cell line, Treatment
View SamplesTranscriptomes of mouse embryonic autopods were generated detecting expression of approximately 26179 transcripts in the developing forelimb or hindlimb autopods, representing about 58 % of the probe sets on MOE-430 A/B GeneChip. Three biological replicate array experiments were finished for each condition and MAS5.0 signal were used to do data analysis. Forty-four transcripts with expression differences higher than 2-fold were detected(T test, P<0.05), including Tbx4, Tbx5, Hoxc10 and Pitx1 which were previously shown to be differentially expressed in developing forelimb and hindlimb bud by in situ hybridization and SAGE study (Margulies 2001). RTPCR and in situ experiments confirmed several top differentially expressed genes which were newly discovered by our experiments. Vast amount of transcripts and its family members such as Bmp, Fgf, Epha, Wnt, T-box and Hox families detected to be highly expressed or differentially expressed in developing autopods, suggesting that the complexity of transcriptomes of developing autopods and dynamic differential expression and differential combinations of gene expression signals in the developing limb tissue contributes to differences in forelimb versus hindlimb patterning. The differentially expressed genes are the essential factors for morphological diversification of developing limb structures.
Transcriptome analysis of the murine forelimb and hindlimb autopod.
No sample metadata fields
View Samples