The development, homeostasis and function of B lymphocytes involve multiple rounds of B cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. Conditional Zfx deletion in the bone marrow blocked B cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused impaired generation of the B-1 cell lineage, accelerated B cell turnover, depletion of mature recirculating cells, and delayed T-dependent antibody responses. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival. This was accompanied by aberrantly enhanced and prolonged integrated stress response, and delayed induction of Cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to B cell expansion and maintenance during development and peripheral homeostasis.
Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes.
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Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
Specimen part, Cell line, Time
View SamplesWe describe a novel subset of CD8+ DCs in lymphoid organs of nave mice characterized by expression of the CX3CR1 chemokine receptor. CX3CR1+CD8+ DCs lack hallmarks of classical CD8+ DCs, including IL12 secretion, the capacity to cross-present antigen and their developmental independence of the transcriptional factor BatF3. Gene expression profiling showed that CX3CR1+CD8+ DCs resemble CD8- cDCs. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX3CR1+ CD8+ DCs. A PDC relationship of the cells is further supported by the fact that they harbor characteristic D-J immunoglobulin gene rearrangements and that development of CX3CR1+CD8+ DCs requires E2-2, the critical transcriptional regulator of PDCs. Thus, CX3CR1+ CD8+ DCs represent a unique DC subset, related to but distinct from PDCs.
CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells.
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View SamplesAnalysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
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View SamplesEndogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neuron. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. Overall design: DEG analysis of primary OPC and OL populations, 5 biological replicates per population
Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation <i>In Vitro</i>.
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View SamplesIt is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor 1 (TGF) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma, previously divested of endogenous epithelia, of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGF activity is a key mechanism of tumor promotion.
Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Age, Specimen part
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Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sex
View SamplesRNAseq analysis of cloche m39 mutant zebrafish embryos and wild type siblings at 90% epiboly - tailbud stage Overall design: In order to isolate the cloche gene, RNAseq was performed on a deletion allele of the zebrafish cloche mutant. RNA was extracted from individual embryos at a stage the cloche gene was predicted to be expressed based on previous literature. RNA from the respective genoptypes was then pooled and subjected to RNAseq analysis.
Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.
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View SamplesSTEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips.
Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on RNA expression in vivo and in vitro.
Sex, Specimen part, Treatment
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Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line, Treatment
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