Role of Notch signaling in the mammalian heart

Zhou, Xueliang; Liu, J.C.

doi:10.1590/1414-431x20133177

Cited by 48 publications

(36 citation statements)

References 60 publications

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“…2, Additional file 3: Table S4). Overall, our results indicate significant enrichment of signaling pathways including Notch, ErbB and NF-κB signaling pathways that recent studies have associated with CHD [2,3], as well as opioid, neuregulin, gap junction, VEGF, and FAK signaling pathways that were previously associated with heart disease [51][52][53][54][55][56][57].…”

Section: Gene Enrichment and Pathway Analyses Chd Dnvs Are Enriched Isupporting

confidence: 63%

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

et al. 2020

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Background: Congenital heart disease (CHD) affects~1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD. Methods: CHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant-and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization. Results: Our analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHDcausing genes. Conclusions: Ultimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.

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Section: Gene Enrichment and Pathway Analyses Chd Dnvs Are Enriched Isupporting

confidence: 63%

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

et al. 2020

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“…Control of expression of this Notch receptor gene might be related to its involvement in the repair of injury to adult heart by increasing myocyte survival, decreasing myocyte hypertrophy, controlling cardiogenic differentiation, and inhibiting fibrosis 44 . In mature brain, which also had high levels of 5hmC at this NOTCH1 site, NOTCH1 has been implicated in the control of cell fate decisions in adult stem and progenitor cells 45 …”

Section: Discussionmentioning

confidence: 99%

Notch signaling genes

et al. 2014

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Notch intercellular signaling is critical for diverse developmental pathways and for homeostasis in various types of stem cells and progenitor cells. Because Notch gene products need to be precisely regulated spatially and temporally, epigenetics is likely to help control expression of Notch signaling genes. Reduced representation bisulfite sequencing (RRBS) indicated significant hypomethylation in myoblasts, myotubes, and skeletal muscle vs. many nonmuscle samples at intragenic or intergenic regions of the following Notch receptor or ligand genes: NOTCH1, NOTCH2, JAG2, and DLL1. An enzymatic assay of sites in or near these genes revealed unusually high enrichment of 5-hydroxymethylcytosine (up to 81%) in skeletal muscle, heart, and cerebellum. Epigenetics studies and gene expression profiles suggest that hypomethylation and/or hydroxymethylation help control expression of these genes in heart, brain, myoblasts, myotubes, and within skeletal muscle myofibers. Such regulation could promote cell renewal, cell maintenance, homeostasis, and a poised state for repair of tissue damage.

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“…Genetically, HLHS is characterized by substantial heterogeneity and a complex pattern of inheritance. While the genetic causes of HLHS continue to be explored, recent studies have suggested that left ventricular outflow tract malformations, including HLHS, can be caused by mutations in the NOTCH1 gene, a member of the highly conserved Notch signaling pathway involved mammalian cardiogenesis (McBride et al, ; Hickey et al, ; Iascone et al, ; Zhou and Liu, ; Freylikhman et al, ). In our patient, in addition to the hypoplastic left ventricle, there was moderate mitral valve hypoplasia, a dysplastic aortic valve, and severe transverse aortic arch hypoplasia.…”

Section: Discussionmentioning

confidence: 99%

Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic left heart syndrome and 9q34.3 microdeletion

Campbell

Collins

Zárate

2014

Birth Defects Research

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Kleefstra syndrome is a multisystem disorder with a high frequency of congenital heart disease and less frequently, renal defects. Mortality has rarely been documented, particularly in infancy. Based on the present case and the extant literature, a routine echocardiogram and renal ultrasound should be ordered in all cases of Kleefstra syndrome. The cardiac changes seen in this patient could be the result of the haploinsufficiency of EHMT1, NOTCH1, or their combined effect.

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Role of Notch signaling in the mammalian heart

Cited by 48 publications

References 60 publications

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

Notch signaling genes

Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic left heart syndrome and 9q34.3 microdeletion

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