Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
Human Lacrimal Gland Gene Expression.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development.
Specimen part
View SamplesThe 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.
Specimen part, Cell line
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 SamplesFOXO1 is highly expressed in normal B cells and in most types of non-Hodgkinl lymphoma. In Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma(cHL) expression of FOXO1 is low or absent. We overexpressed constitutively active mutant of FOXO1 fused in frame with estrogen receptor ligand-binding domain (FOXO1(3A)ER), which can be activated by 4-Hydroxytamoxifen (4-OHT), in cHL cell lines KM-H2 and L428. Activation of the FOXO1 with 4-OHT resulted in inhibition of proliferation and apoptosis. Using gene-expression array we found that FOXO1 activates transcription of known and potential tumor suppressor genes: CDKN1B, PMAIP1, BCL2L11, TNFSF10, FBXO32, CBLB). Of note, FOXO1 repressed transcription of several cytokines and cytokine receptors, which are known tobe involved in pathogenesis of cHL (e.g. CCL5, CXCR5, TNFRSF8). Taken togather our data indicate important role of FOXO1 repression in pathogenesis of cHL.
FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.
Specimen part, Cell line, Treatment
View SamplesGliogenesis in the Drosophila CNS occurs during embryogenesis and also during the postembryonic larval stages. Several glial subtypes are generated in the postembryonic CNS through the proliferation of differentiated glial cells. The genes and molecular pathways that regulate glial proliferation in the postembryonic CNS are poorly understood. In this study we aimed to use gene expressing profiling of CNS tissue enriched in glia to identify genes expressed in glial cells in the postembryonic CNS.
Glial enriched gene expression profiling identifies novel factors regulating the proliferation of specific glial subtypes in the Drosophila brain.
Specimen part
View SamplesAblation of the mouse gene for Onecut-2 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here, we examine postnatal development of these Onecut-2 knockout mice, especially the critical period prior to weaning. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in the Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression.
Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine.
Sex, Specimen part
View SamplesWe compared four transcription factor knockdowns using transgenic RNAi expressed in the larval fat body. FOXO, Tfb1, p53, and Stat92E-dependent gene expression in the Drosophila fat body was quantified on control and high-sugar diets in order to generate expression profiles via RNA-seq. These expression data were used to build a gene regulatory network to predict novel roles for these and other genes during caloric overload. Overall design: Control and fat body-expressed transcription factor RNAi Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M or 1M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sex, Specimen part, Treatment, Subject
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