The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into -cells. The induced -cells resemble islet -cells in morphology and histology, express genes essential for -cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
Specimen part, Treatment
View SamplesMemory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their nave precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells in order to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of antigen-specific memory and nave cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors.
Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities.
No sample metadata fields
View SamplesHemophagocytes are activated macrophages seen morphologically to have engulfed other hematopoietic cells. Their function is unknown. Attempts to induce these cells in vitro or purify them ex vivo have been unsuccessful.
Brief report: alternative activation of laser-captured murine hemophagocytes.
Sex, Age, Specimen part
View SamplesWe''ve recently shown that we can accelerate disease in a model of SLE (the NZB/W F1 model) using an anti-Ox40 mAb treatment regimen. The disease acceleration is rapid (within 2 weeks) but its unclear, mechanistically, how OX40 functions to promote disease. To that end we want to perform RNASeq on the sorted OX40-expressing CD4 T cells during treatment to understand how they function in response to OX40 signaling in vivo Overall design: RNASeq was performed on FACS sorted CD4 T cells from the spleen and kidney of NZB/W F1 lupus mice following anti-Ox40 agonist mAb treatment and disease acceleration
The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.
Cell line, Treatment, Subject
View SamplesWe''ve recently shown that we can accelerate disease in a model of SLE (the NZB/W F1 model) using an anti-Ox40 mAb treatment regimen. The disease acceleration is rapid (within 2 weeks) but its unclear, mechanistically, how Ox40 promotes disease. To that end we performed RNASeq on in vitro cultured CD4 T cells during Ox40 and TCR stimulation (in a reductionist setting) to understand how Ox40 signaling impacts cellular phenotype and function, including with and without TCR stimulation Overall design: RNASeq was performed on in vitro cultured CD4 T cells from the spleen of NZB/W F1 lupus prone mice, following anti-Ox40 mAb and anti-CD3/CD28 bead stimulation
The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.
Cell line, Subject
View Samplesgamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray.
Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury.
No sample metadata fields
View SamplesMyeloid progenitors derived from antibiotic-treated mice have cell-intrinsic functional defects. In this microarray dataset, the transcriptomes of bone marrow myeloid progenitors from antibiotic-treated and control mice are compared.
Microbiota-dependent signals are required to sustain TLR-mediated immune responses.
No sample metadata fields
View SamplesThis study delineated how small intestinal resident microflora impact gene expression in Paneth cells.
Symbiotic bacteria direct expression of an intestinal bactericidal lectin.
No sample metadata fields
View SamplesFbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-mediated substrate degradation is antagonized by the Usp28 deubiquitinase. We now show, using knockout mice, that Usp28 preferentially deubiquitinates and stabilizes Fbw7. Monoallelic deletion of Usp28 maintains stable Fbw7 but destabilizes Fbw7 substrates. In contrast, complete knockout of Usp28 promotes Pin1-dependent autocatalytic turnover of Fbw7, accumulation of Fbw7 substrates and oncogenic transformation. Overexpression of Usp28 stabilizes both Fbw7 and its substrates and similarly enhances transformation. We propose that dual regulation of Fbw7 activity by Usp28 maintains physiological levels of Fbw7 substrates, and that both loss and overexpression of Usp28 in human cancer promote Fbw7 substrate accumulation. Overall design: RNAseq experiments of E13.5 murine embryonic fibroblasts (MEFs) derived from animals in which Usp28 was either deleted (-/-), wildtype (+/+) or heterozygous (+/-). In a first set of experiments immortalized MEFs of all three genotypes were analysed in biological triplicates. In a second set of experiments immortalized and Ras transformed MEFs of all three genotypes and MEFs which overexpress USP28 (+/+/+) where sequenced in duplicates.
Dual regulation of Fbw7 function and oncogenic transformation by Usp28.
No sample metadata fields
View SamplesGenes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal, immortalized, transformed and tumorigenic bronchial epithelial cells were identified. The differentially expressed genes were then analyzed to determine their relevance to the gene expression patterns of clinical non-small cell lung cancer (NSCLC) samples as well as the clinical outcome of patients with this disease.
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
Cell line
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