HMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Specimen part, Treatment
View SamplesThe retinal pigment epithelial (RPE) cell line ARPE-19 provides a widely-used alternative to native RPE. However, retention of the native RPE phenotype becomes problematic after multiple passages. We wished to determine if suitable culture conditions and differentiation could restore RPE-appropriate gene expression to ARPE-19. ARPE-19 cells at passages p9 to p12, grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum, were differentiated for up to 4 months. Using RNA-Seq, we compared the transcriptome of ARPE-19 cells kept in long-term culture with those cultured for 4 days. The 4 month cells developed the classic native RPE phenotype with heavy pigmentation. RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of genes in the 4 month cells. Of the 16,757 genes with detectable signals, nearly 2435 genes were upregulated, and 931 genes were down-regulated with a fold change differences of 2 or more. Genes characteristic of RPE, including RPE65, RDH5 and RDH10, were greatly increased in ARPE-19 cells maintained at confluence for 4 months. Comparison with microarray data sets from human primary cell lines revealed important overall similarities in expression of "signature" genes. The results of this study demonstrate that ARPE-19 cells can express genes specific to native human RPE cells when appropriately cultured, and thus, can provide a relevant system to study differentiated cellular functions of RPE in vitro. Overall design: RNA-Seq profiles of ARPE-19 cells grown for 4 days or 4 months; triplicate replicates were sequenced.
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
Specimen part, Cell line, Subject
View SamplesChromatin architectural protein NSBP1/HMGN5 belongs to the family of HMGN proteins which specifically interact with nucleosomes via Nucleosome Binding Domain, unfold chromatin and affect transcription. Mouse NSBP1 is a new and uncharacterized member of HMGN protein family. NSBP1 is a nuclear protein which is localized to euchromatin, binds to linker histone H1 and unfolds chromatin.
The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription.
No sample metadata fields
View SamplesMicroarray experiments were performed using FAC-sorted young photoreceptors to analyze their transcriptome in comparison to remaining retinal cells at same developmental stage and retinal progenitors.
Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina.
Specimen part
View SamplesPathologic and epidemiologic evidence has led to a histologic model of breast cancer progression that involves advancement through specific morphologic stages including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Numerous observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these different stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series. We report here that three of the 21T cell lines indeed mimic specific stages of human breast cancer progression (21PT-derived cells, ADH; 21NT-derived cells, DCIS; 21MT-1 cells, IMC) when grown in the mammary fat pad of nude mice, albeit after up to a year post-injection. In order to develop a more rapid, readily manipulatable in vitro assay for examining the biologic differences between these cell lines, we have made use of a 3D Matrigel system. When grown in 3D Matrigel, we have found characteristic morphologies of the three cell lines in which quantifiable aspects of the stage-specific in vivo behaviors (i.e. differences in acinar structure formation, cell polarization, cell cohesiveness, cell proliferation, cell invasion) are re-capitulated in a reproducible fashion. Gene expression profiling has revealed a characteristic pattern for each of the three cell lines. Interestingly, WNT pathway alterations are particularly predominant in the early transition from 21PTci (ADH) to 21NTci (DCIS), whereas alterations in expression of genes associated with control of cell motility and invasiveness phenomena are more prominent in the later transition of 21NTci (DCIS) to 21MT-1 (IMC). This system thus reveals potential therapeutic targets and will provide a means of testing the influences of identified genes on transitions between these stages of pre-malignant to malignant growth.
Human 21T breast epithelial cell lines mimic breast cancer progression in vivo and in vitro and show stage-specific gene expression patterns.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View SamplesExtraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 g T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View SamplesExtraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 g T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View Samplesusing RNA-seq we characterized gene expression changes occuring upon knockout of BAP1, ASXL1, ASXL2, ASXL1/2 or Polycomb genes RING1B and EZH2. We also investigated the response to retinoic acid treatment in wild-type and BAP1 KO cells. Overall design: Examination of transcript abundance in wild-type HAP1 cells and in 9 different HAP1-mutated cell lines as well as upon retinoic acid treatment in wild-type and BAP1 KO cells. Two biological replicated were performed for each condition.
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Cell line, Treatment, Subject
View SamplesCharacterization of gene expression changes occuring upon knockout of RING1A, RING1B, and BAP1. Overall design: Four Samples
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Specimen part, Treatment, Subject
View Samples