NIPBL
| Autor: | Jason A, Mills, Pamela S, Herrera, Maninder, Kaur, Lanfranco, Leo, Deborah, McEldrew, Jesus A, Tintos-Hernandez, Ramakrishnan, Rajagopalan, Alyssa, Gagne, Zhe, Zhang, Xilma R, Ortiz-Gonzalez, Ian D, Krantz |
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| Rok vydání: | 2017 |
| Předmět: |
Heart Defects
Congenital Pluripotent Stem Cells Genotype Gene Expression Profiling Induced Pluripotent Stem Cells Computational Biology Proteins Cell Cycle Proteins Cell Differentiation Haploinsufficiency Article Gene Expression Regulation De Lange Syndrome Humans Genetic Predisposition to Disease Myocytes Cardiac Transcriptome Biomarkers Myoblasts Cardiac |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/− patient-derived cells. We demonstrate that NIPBL haploinsufficiency leads to upregulation of gene sets identified in functions related to nucleosome, chromatin assembly, RNA modification and downregulation of Wnt signaling, cholesterol biosynthesis and vesicular transport in iPSC and cardiomyocytes. Mutations in NIPBL result in the dysregulation of many genes responsible for normal heart development likely resulting in the variety of structural cardiac defects observed in the CdLS population. |
| Databáze: | OpenAIRE |
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