The AIL transcription factor BABY BOOM (BBM) is required together with the related PLETHORA proteins for embryo and root meristem development and its expression is sufficient to confer pluripotency and totipotency to somatic tissues. We show that BBM and other AIL proteins interact with multiple members of the L1/epidermal-expressed HD-ZIP class IV / HOMEODOMAIN GLABROUS (HDG) transcription factor family. Ectopic overexpression of HDG1, HDG11 and HDG12 genes induces a reduced growth phenotype, and analysis of HDG1 overexpression lines shows that this growth reduction is due to both root and shoot meristem arrest. To understand how HDG1 controls cell proliferation, as well as its functional relationship with BBM, we performed microarray experiments to identify candidate genes that are directly regulated by HDG1, and compared these to the set of genes that are directly regulated by BBM expression.
AIL and HDG proteins act antagonistically to control cell proliferation.
Specimen part, Treatment
View SamplesMalignant mesothelioma (MM) is an asbestos-related malignancy and largely unresponsive to conventional chemotherapy or radiotherapy. Novel, more effective therapeutic strategies are needed for this fatal disease. We performed microarray analysis of MM using Affymetrix Human U133 Plus 2.0 array. Aberrant expression of the genes participating in semaphorin signaling were detected in malignant mesothelioma cells. All MM cells downregulated the expression of more than one gene for SEMA3B, 3F, and 3G when compared with Met5a, a normal pleura-derived cell line. In 12 of 14 epithelioid MM cells, the expression level of SEMA3A was lower than that in Met5a. An augmented expression of VEGFA was detected in half of the MM cells. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a and the non-epithelioid MMs. Next, gene expression profiling for the polycomb and trithorax group genes revealed that expression of BAP1, the catalytic subunit of the polycomb repressive deubiquitinase complex, and many trithorax group genes was downregulated in MMs compared with the expression of the same genes in Met5a cells. Perturbation of the polycombtrithorax balance plays a significant role in the pathogenesis of malignant mesothelioma.
Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.
Sex, Age, Specimen part, Cell line
View SamplesWe sought to characterize expression profiles signifying the development of atypical adenomatous hyperplasia (AAH) from normal lung parenchyma (NL), and its progression to lung adenocarcinomas (LUAD). Overall design: We performed transcriptome sequencing of 48 samples, comprising NLs, AAHs and LUADs, from 17 patients. Sequencing was performed using the Ion Torrent platform afterwhich gene profiles differentially expressed among the three groups were determined.
Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma.
Specimen part, Subject
View SamplesTobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.
Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.
Sex, Age
View SamplesLactic acid bacteria confer a variety of health benefits. Here we investigate the mechanisms by which Lactobacillus brevis KB290 enhances cell-mediated cytotoxic activity. We fed a diet containing KB290 (3 10^9 colony-forming units/g) , or potato starch, to 9-week-old female BALB/c mice for 1, 4, 7, or 14 days and examined the cytotoxic activity of splenocytes was measured. RNA was extracted from the spleen and analyzed for gene expression by DNA microarray.
Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.
Sex, Age, Specimen part
View SamplesPersistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Cell line
View SamplesiPSC-derived NSPCs, which were induced by two different protocols (Embryoid body or Neural rosette) followed by expansion in free-floating culture (neurospheres), had closely resembled profiles.
Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.
Sex, Race
View SamplesThe entire small intestine was obseved by balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.
Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease.
Specimen part, Disease, Disease stage
View SamplesWe have previously established an in vitro tissue culture system (named VISUAL; Kondo et al., 2016), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
BES1 and BZR1 Redundantly Promote Phloem and Xylem Differentiation.
Specimen part, Treatment, Time
View SamplesXylem consists of three types of cells: vessel cells, also referred to as tracheary elements (TEs), parenchyma cells, and fiber cells. TE differentiation includes two essential processes, programmed cell death (PCD) and secondary cell wall formation. These two processes are tightly coupled. However, little is known about the molecular mechanism of their gene regulation. Here, we show that VASCULAR-RELATED NAC-DOMAIN 6 (VND6), a master regulator of TEs, regulates these processes in a coordinated manner. We first identified specific genes downstream of VND6 by comparing them with those of SECONDARY WALL-ASSOCIATES NAC DOMAIN PROTEIN1 (SND1), a master regulator of xylem fiber cells, with transformed suspension culture cells in microarray experiments.
Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 directly regulates the genes that govern programmed cell death and secondary wall formation during xylem differentiation.
Time
View Samples