In this experiment, we sought to analyze how the transcriptome of WT, ?5|6, and ?5|6:7|9 cells vary during differentiation of ESCs into cervical motor neurons Overall design: 3 lines (WT, ?5|6, ?5|6:7|9)
CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.
No sample metadata fields
View SamplesProductive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa () or lambda () light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the 3 and enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells.
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
No sample metadata fields
View SamplesThe chromatin regulator Aiolos and the transcriptional coactivator OBF-1 have been implicated in regulating aspects of B cell maturation and activation. Mice lacking either of these factors have a largely normal early B cell development. However, when both factors are eliminated simultaneously a block is uncovered at the transition between pre-B and immature B cells, indicating that these proteins exert a critical function in developing B lymphocytes. In mice deficient for Aiolos and OBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulin light chain DNA rearrangement is observed. We identified genes whose expression is deregulated in the pre-B cell compartment of these mice. In particular, we found that components of the pre-BCR, such as the surrogate light chain genes l5l5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the l5l5 gene is impaired in pre-B cells lacking OBF-1 and Aiolos. These studies uncover a novel role for OBF-1 and Aiolos in controlling the transcription and nuclear organization of genes involved in pre-BCR function.
Silencing and nuclear repositioning of the lambda5 gene locus at the pre-B cell stage requires Aiolos and OBF-1.
No sample metadata fields
View SamplesWe report differences in gene expression between WT and Bmi1 KO pro-B cells. Overall design: RNA profiles from WT and Bmi1 KO pro-B cells were generated in duplicate.
Impaired Expression of Rearranged Immunoglobulin Genes and Premature p53 Activation Block B Cell Development in BMI1 Null Mice.
Specimen part, Cell line, Subject
View SamplesExpression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
Specimen part
View SamplesAtopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. The goal of this study was to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.
Specimen part, Disease
View SamplesWe report that in developing B cells individual enhancers of Igk make up super-enhancer cluster where contacts between its components rely on all constituents. Reduction of interaction frequency in enhancer knock-out cells is associated with deminished transcriptional output of enhancers and Igk locus. Moreover, we find that Igk enhancer MiEk has an effect on levels of CBFb enrichment on Tcrb enhancer, Eb afffecting Tcrb recombination and T cell development. Overall design: Examination of expression, chromatin accessibility, histone modifications and nuclear organization in developing wild-type and Igk and Tcrb enhancer deficient B and T lymphocytes.
Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.
Specimen part, Cell line, Subject
View SamplesClassical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC, that is not expressed by other immune cell populations, including pDCs, monocytes, or macrophages. Here we define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, upregulates activation pathways in steady state cDCs including elevated MHC II expression, and enhances cDC production of VEGF leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly downregulated after TLR ligation. Thus, zDC is a TLR-responsive cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state.
Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Sex, Specimen part, Cell line, Treatment
View SamplesExpression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation.
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Specimen part, Cell line, Treatment
View Samples