The transcription factor IRF4 regulates immunoglobulin class switch recombination and plasma cell differentiation. Its differing concentrations appear to regulate mutually antagonistic programs of B and plasma cell gene expression. We show IRF4 to be also required for generation of germinal center (GC) B cells. Its transient expression in vivo induced the expression of key GC genes including Bcl6 and Aicda. In contrast, sustained and higher concentrations of IRF4 promoted the generation of plasma cells while antagonizing the GC fate. IRF4 cobound with the transcription factors PU.1 or BATF to Ets or AP-1 composite motifs, associated with genes involved in B cell activation and the GC response. At higher concentrations, IRF4 binding shifted to interferon sequence response motifs; these enriched for genes involved in plasma cell differentiation. Our results support a model of "kinetic control" in which signaling-induced dynamics of IRF4 in activated B cells control their cell-fate outcomes.
Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4.
Specimen part, Treatment
View SamplesTemporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.
Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4.
Specimen part, Treatment
View SamplesCell-type specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) sorting of roots that express cell-type specific GFP-reporters. Four different GFP-reporter lines were utilized allowing us to obtain transcriptional profiles for cells in major radial zones of the root. FACS cell populations were isolated from roots grown under standard conditions or roots that had been transfered to media supplemented with 140 mM NaCl for 1 hour, 3 hours, 8 hours, 20 hours, 32 hours and 48 hours.
A spatio-temporal understanding of growth regulation during the salt stress response in Arabidopsis.
Specimen part
View SamplesWe report gene expression changes in Cul3 deficient thymic CD4+ T cells
A negative feedback loop mediated by the Bcl6-cullin 3 complex limits Tfh cell differentiation.
Specimen part
View SamplesTranscriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high resolution set of developmental time points within a single Arabidopsis root, and a comprehensive map of nearly all root cell-types. These cell-type specific transcriptional signatures often predict novel cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional connections between disparate cell types. Dominant expression patterns along the roots longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, expression fluctuation along this axis was observed. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these two sets of profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time.
A high-resolution root spatiotemporal map reveals dominant expression patterns.
No sample metadata fields
View SamplesAntigen receptor gene recombination requires stochastic, monoallelic choice of a single variable gene in each lymphocyte progenitor. However, how this occurs remains unknown. Herein, we report that prior to V? to J? gene recombination, Ig? alleles reside within spatially different nuclear niches defined by elongating RNA Polymerase II (e-Pol II) and cyclin D3 complexes assembled on the nuclear matrix. Upon cell cycle exit, and cyclin D3 downregulation, only the V? allele in the more constrained e-Pol II niche was transcribed. Chromatin modeling and single cell RNA-seq revealed that the nuclear niche favored V? flanking CTCF sites, thus shaping the transcribed repertoire. Furthermore, multiple contiguous V?s oriented away from CTCF sites were preferentially transcribed. Cyclin D3 also repressed monoallelic protocadherin and olfactory genes. These studies of Ig? reveal a general mechanism by which regulated, stochastic chromatin loop capture by fixed e-Pol II complexes generates diversity and couples cell cycle exit to monogenic choice. Overall design: Bulk and Single Cell RNA-seq of B6 x CAST F1 hybrid small pre-B cells and bulk RNA-seq of Ccnd3-/- pro-B cells
Regulated Capture of Vκ Gene Topologically Associating Domains by Transcription Factories.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell identity mediates the response of Arabidopsis roots to abiotic stress.
No sample metadata fields
View SamplesCell-type specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) sorting of roots that express cell-type specific GFP-reporters. Six different GFP-reporter lines were utilized allowing us to obtain transcriptional profiles for cells in all radial zones of the root. FACS cell populations were isolated from roots grown under standard conditions or roots that had been transfered to media supplemented with 140 mM NaCl for 1 hour.
Cell identity mediates the response of Arabidopsis roots to abiotic stress.
No sample metadata fields
View SamplesTo gain a genome-scale understanding of the role that developmental processes play in regulating stimulus response, we examined the effect of salt stress on gene expression along the longitudinal axis of the root. Since roots grow from stem cells located near the tip, the position of cells along the longitudinal axis can be used as a proxy for developmental time, with distance from the root tip correlating with increased differentiation. To estimate the role developmental stage plays in regulating salt response, roots were dissected into four longitudinal zones (LZ data set) after transfer to standard or salt media and transcriptionally profiled.
Cell identity mediates the response of Arabidopsis roots to abiotic stress.
No sample metadata fields
View SamplesWe performed an expression analysis of the response of seedling root tips to 1 hour of treatment with 140mM NaCl using mutants defective in root hair patterning.
Cell identity mediates the response of Arabidopsis roots to abiotic stress.
No sample metadata fields
View Samples