ABSTRACT
Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.
Subject(s)
Embryonic Stem Cells/metabolism , Gene Expression , Pluripotent Stem Cells/metabolism , Animals , Cell Line , DNA Methylation , Embryonic Stem Cells/cytology , Gene Expression Profiling , Genomic Instability , Histones/genetics , Humans , Mice , MicroRNAs/metabolism , Pluripotent Stem Cells/cytology , Promoter Regions, GeneticABSTRACT
Differences between individual DNA sequences provide the basis for human genetic variability. Forms of genetic variation include single-nucleotide polymorphisms, insertions/duplications, deletions, and inversions/translocations. The genome of human embryonic stem cells (hESCs) has been characterized mainly by karyotyping and comparative genomic hybridization (CGH), techniques whose relatively low resolution at 2-10 megabases (Mb) cannot accurately determine most copy number variability, which is estimated to involve 10%-20% of the genome. In this brief technical study, we examined HSF1 and HSF6 hESCs using array-comparative genomic hybridization (aCGH) to determine copy number variants (CNVs) as a higher-resolution method for characterizing hESCs. Our approach used five samples for each hESC line and showed four consistent CNVs for HSF1 and five consistent CNVs for HSF6. These consistent CNVs included amplifications and deletions that ranged in size from 20 kilobases to 1.48 megabases, involved seven different chromosomes, were both shared and unique between hESCs, and were maintained during neuronal stem/progenitor cell differentiation or drug selection. Thirty HSF1 and 40 HSF6 less consistently scored but still highly significant candidate CNVs were also identified. Overall, aCGH provides a promising approach for uniquely identifying hESCs and their derivatives and highlights a potential genomic source for distinct differentiation and functional potentials that lower-resolution karyotype and CGH techniques could miss. Disclosure of potential conflicts of interest is found at the end of this article.
Subject(s)
Embryonic Stem Cells/cytology , Embryonic Stem Cells/physiology , Genetic Variation , Genome, Human , Cell Culture Techniques , Cell Division/genetics , DNA/genetics , DNA-Binding Proteins/genetics , Heat Shock Transcription Factors , Heat-Shock Proteins/genetics , Humans , Neurons/cytology , Neurons/physiology , Nucleic Acid Hybridization/methods , Polymerase Chain Reaction/methods , Transcription Factors/geneticsABSTRACT
BACKGROUND & AIMS: Heartburn and gastroesophageal reflux disease (GERD) during pregnancy are accepted as an innocent condition. The effect of heartburn during pregnancy on the initiation or progress of GERD is not known. We aimed to determine the predisposition effect of heartburn during pregnancy for presenting with GERD in the future. METHODS: A validated reflux questionnaire was applied to 1180 randomly selected women aged between 18-49 years who had given birth to at least one delivery. Frequent symptoms were defined as a major symptom (heartburn and/or regurgitation) occurring at least once a week or more. Occasional symptoms were defined as an episode of one of the major symptoms occurring less than once a week within the past 12 months. RESULTS: The mean live delivery rate was 2 +/- 1 (range, 1-10). The prevalence of GERD was 7.4%. Whereas the prevalence of GERD for women with a history of just 1 delivery was 1.5%, more than 2 deliveries were accompanied with risk of 15.1% (P < .001). In the group with no heartburn during pregnancy only 5.5% had GERD (P < .00001). If there was heartburn during any of the pregnancies, the risk was 17.7%; and more than 2 pregnancies with a history of heartburn accompanied 36.1% risk of having GERD. Logistic regression analysis showed that the risk is independent from obesity and age. CONCLUSIONS: The risk of GERD is increased by the presence of heartburn during pregnancy. This association is independent of obesity and age. Heartburn during pregnancy might not be accepted as an innocent and temporary condition.