Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease

Martí-Gómez, Carlos; Larrasa-Alonso, Javier; López-Olañeta, Marina; Villalba-Orero, María; García‐Pavía, Pablo; Sánchez-Cabo, Fátima; Lara‐Pezzi, Enrique

doi:10.1007/s12265-022-10244-x

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…Additionally, principal component analysis has proven to be a powerful tool to summarize alterations in the alternative splicing landscape 6,[27][28][29] . Using SplicePCA, researchers can select splice events for specific genes, integrate their data, and interpret their results in the context of cortical development and specific neuronal cell types.…”

Section: Application and Discussionmentioning

confidence: 99%

“…We offer easily interpretable summaries and visualization of results that allow a broad range of scientists to explore the expression and AS patterns of individual genes. Additionally, we developed SplicePCAa tool that performs a principal component analysis of splicing events for a selected gene set and enables the investigation of splicing patterns related to developmental changes or variations across cell types 6,[27][28][29] . All standardized datasets included in Cortexa are publicly available for download, allowing users to integrate them into their research easily.…”

Section: Introductionmentioning

confidence: 99%

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Cortexa – a comprehensive resource for studying gene expression and alternative splicing in the murine brain

Weißbach,

Milkovits,

Pastore

et al. 2024

Preprint

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Motivation: Gene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate developing harmonized data handling and processing pipelines which in turn require considerable computational resources and in-depth bioinformatics expertise. Results: Here, we present Cortexa - a comprehensive web portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform also provides SplicePCA - a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All gene expression and alternative splicing data have been processed in a standardized manner and they can also be downloaded for further in-depth downstream analysis.

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Section: Application and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cortexa – a comprehensive resource for studying gene expression and alternative splicing in the murine brain

Weißbach,

Milkovits,

Pastore

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…These changes are associated with a highly coordinated alternative splicing program that produces substantial protein isoform transitions that play critical roles in - postnatal heart growth and maturation [ 47 ]. Using bulk RNA sequencing, transcriptome dynamics in mouse heart cells, cardiomyocytes, and cardiac fibroblasts, at different prenatal and postnatal stages were recently revealed [ 48 ]. While significant splicing changes in cardiomyocytes occur within the first month after birth, indicating an important role of alternative splicing in cardiomyocyte maturation, splicing transitions in cardiac fibroblasts continue beyond the first month.…”

Section: Alternative Splicing Transition During Heart Developmentmentioning

confidence: 99%

Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects

Mehta

Touma

2023

IJMS

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Advancements in genomics, bioinformatics, and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts were directed toward investigating this process in heart development and failure. However, few studies shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports showed the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs. Wediscuss the impact of perinatal splicing transition and its dysregulation in CHDs. We further summarize the discoveries made of causal splicing variants in key transcription factors that are implicated in CHDs. An improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

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“…Using bulk RNA-sequencing, transcriptome dynamics in mouse heart cells, cardiomyocytes and cardiac fibroblasts, at different prenatal and postnatal stages were recently revealed [48]. While significant splicing changes in cardiomyocytes occur within the first month after birth indicating an important role of alternative splicing in cardiomyocyte maturation, splicing transitions in cardiac fibroblasts continue beyond the first month.…”

Section: Alternative Splicing Transition During Heart Developmentmentioning

confidence: 99%

Post-Transcriptional Modification by Alternative Splicing in Cardiovascular Development and Congenital Heart Defects

Mehta¹,

Touma²

2022

Preprint

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Advancements in genomics, bioinformatics and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts have been directed towards investigating this process in heart development and failure. However, few studies have shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports have shown the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs and discuss the impacts of perinatal splicing transition and its dysregulation in CHDs. We further summarize discoveries made of causal splicing variants in key transcription factors that have been implicated in CHDs. Improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

show abstract

Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease

Cited by 10 publications

References 46 publications

Cortexa – a comprehensive resource for studying gene expression and alternative splicing in the murine brain

Cortexa – a comprehensive resource for studying gene expression and alternative splicing in the murine brain

Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects

Post-Transcriptional Modification by Alternative Splicing in Cardiovascular Development and Congenital Heart Defects

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