AID-dependent U/G mismatches in S DNA are converted by BER and MMR DNA pathways into double-stranded breaks that are required for optimal CSR in activated B cells. Deficits in MMR proteins, MSH2, MLH1, and PMS2 result in lower CSR frequencies that are coupled with impaired DSB formation. MBD4 interacts with MLH1 and has been postulated to coordinate mismatch repair of U/G. Deletions of Mbd4 targeting the 5' end of the gene in mice do not affect CSR . However, Mbd4 transcription is complex, with the propensity to create alternative transcripts, including residual transcription leading to to truncated protein expression that complicates ananlysis in these mice. We describe a novel function of MBD4 housed in the C-terminus that is critical for DSB formation, which shares several characteristics with MMR . We conclude that the 3' end of the Mbd4 gene positively contributes to CSR and likely intersects the MMR pathway.
MBD4 Facilitates Immunoglobulin Class Switch Recombination.
Cell line, Treatment
View SamplesThe discovery of activity-dependent neuroprotective protein (ADNP) regulated tooth eruption in mice and man, provides, for the first time, an early detection of tooth eruption, with full or almost full mouth of teeth at one year of age, as a potential biomarker for an intellectual disability (ID)/autism spectrum disorder (ASD) syndrome, toward improved translational medicine. Overall design: RNAseq of 4 samples, comparing three ADNP-mutated lymphoblastoid cell lines (LCLs, derived from ADNP-mutated children) with a non-mutated cell line. No replicates were performed but results were verified usign RT-PCR.
Tauopathy in the young autistic brain: novel biomarker and therapeutic target.
Specimen part, Cell line, Subject
View SamplesA key function of Na+/H+ exchanger regulatory factor 2 (NHERF2) is spatial organization of signaling proteins to facilitate signal transduction. The role of NHERF2 in cancer progress is not well understood. This study determines how loss of NHERF2 alter colon cancer progress. Overall design: We show that loss of NHERF2 decreases colon cancer cell proliferation. To compare the effects of NHERF2 and LPA2 at the molecular level, HCT116 colon cancer xenograft with knockdown of NHERF2 or LPA2 was analyzed by RNAseq. Please note that standard cufflinks/cuffdiff output files are provided in the compressed tar files as processed data and Cufflinks/Cuffdiff output file content/formats are described at: https://cole-trapnell-lab.github.io/cufflinks/cuffdiff/#cuffdiff-output-files https://cole-trapnell-lab.github.io/cufflinks/file_formats/ (also included in the ''readme.txt'' file)
Deletion of Na+/H+ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24.
No sample metadata fields
View SamplesPrevious studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Cell line
View SamplesThis series contain mouse and rat lung samples treated with mechanical ventilation and corresponded controls.
Bioinformatic identification of novel early stress response genes in rodent models of lung injury.
No sample metadata fields
View SamplesIdentification of genes regulated by the transcription factor HNF4a2
HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma.
No sample metadata fields
View SamplesThis analysis represents the first comprehensive sampling of germ cells in the developing testis over time, at high-resolution, single-cell depth. From these analyses, we have not only revealed novel genetic regulatory signatures of murine germ cells over time, but have also demonstrated that cell types positive for a single marker gene have the capacity to change dramatically during testis maturation, and therefore cells of a particular “identity” may differ significantly from postnatal to adult life. Overall design: Single-cell suspensions of mammalian testes ranging from PND6 to adult were processed for single-cell RNAseq (10x Genomics Chromium) and libraries were sequenced on a NextSeq500 (Illumina).
Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing.
Age, Disease, Cell line, Subject
View SamplesAlzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level we provide evidence that anle138b blocks the formation of conducting Aß pores without changing the membrane embedded Aß-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further. Overall design: APPdelta9 and Wildtype mouse treated with anle138b or placebo
The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
Age, Cell line, Subject
View SamplesExperiments in rodents have shown that kidney ischemia/reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 hours following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n=3/group).
Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy.
No sample metadata fields
View SamplesDrosophila miRNAs show distinct change in isoform distribution pattern with age. Some miRNAs show accumulation of the short isoforms, while other miRNAs show the accumulation of the long isoforms with age. The increase of the long isoforms of some miRNAs reflects increased 2''-O-methylated miRNA isoforms with age. The increase in 2''-O-methylated miRNA isoforms reflected increased Ago2-loading, but not Ago1-loading of specific miRNA isoforms with age. This raised a question on whether there is global shift in small RNA loading pattern between Ago1 and Ago2 with age. To investigate change in small RNA loading pattern between Ago1 and Ago2 with age, we performed small RNA deep-sequencing of Ago1 vs Ago2-IP small RNAs at 3d and 30d in Drosophila. This analysis revealed global increase of miRNA loading into Ago2, but not into Ago1 with age. Overall design: 3d and 30d FLAG-HA-Ago2 male flies were collected. Ago1 and Ago2 were immunoprecipitated by anti-Ago1 and anti-FLAG M2 beads respectively. RNA was purified from the beads, P32-labeled, and small RNA fraction was gel-purififed. Small RNA libraries were prepared using Illumina''s TruSeq small RNA sample preparation kit (#RS-200-0012, Illumina, Inc. San Diego, CA), following the manufacturer''s protocol. The libraries were multiplexed and sequenced on HiSeq2000 platform (Illumina).
Impact of age-associated increase in 2'-O-methylation of miRNAs on aging and neurodegeneration in Drosophila.
Sex, Specimen part, Subject
View Samples