Project description:This SuperSeries is composed of the following subset Series: GSE35490: Noncoding RNA expression in myocardium from infants with tetralogy of Fallot [miRNA profiling] GSE35776: Noncoding RNA expression in myocardium from infants with tetralogy of Fallot [mRNA profiling] Refer to individual Series
Project description:This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants
Project description:This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development.
Project description:This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development.
Project description:Tetralogy of Fallot (TOF) is one of the most common heart defects in children and the underlying mechanisms remain elusive. miRNAs are a recently discovered class of regulators of gene expression and are becoming increasingly recognized as important regulators of heart development and function. The objective of the present study was to identify miRNAs that are abnormally expressed in clinical infant outflow tract myocardium tissues of TOFs. Microarray was used to analyze miRNA expression profiles in infant outflow tract myocardium tissues of TOFs and paired normal ones.
Project description:Tetralogy of Fallot (TOF) is one of the most common heart defects in children and the underlying mechanisms remain elusive. miRNAs are a recently discovered class of regulators of gene expression and are becoming increasingly recognized as important regulators of heart development and function. The objective of the present study was to identify miRNAs that are abnormally expressed in clinical infant outflow tract myocardium tissues of TOFs.
Project description:To determine cardiac transcription profile in acyanotic Tetralogy of Fallot patients, we collected myocardial samples immediately after institution of cardiopulmonary bypass from acyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Myocardial samples were collected, immediately after institution of cardiopulmonary bypass from acyanotic Tetralogy of Fallot patients undergoing corrective surgery.
Project description:To determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients, we collected myocardial samples immediately after institution of cardiopulmonary bypass from cyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Myocardial samples were collected, immediately after institution of cardiopulmonary bypass from cyanotic Tetralogy of Fallot patients undergoing corrective surgery.
Project description:To determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients, we collected myocardial samples immediately after institution of cardiopulmonary bypass from cyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology.
Project description:To determine cardiac transcription profile in acyanotic Tetralogy of Fallot patients, we collected myocardial samples immediately after institution of cardiopulmonary bypass from acyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology.