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Exploring the Dynamics and Consequences of Differential Transcript Usage in Cardiomyocyte Fate Specification

ABSTRACT: Cardiovascular research often relies on in vitro models using induced pluripotent stem cells (iPSCs) differentiating into induced cardiomyocytes (iCM). Little is known about the changes in transcript variants, termed differential transcript usage (DTU), which greatly influence cellular programs. In this study, we explored the DTU landscape during the iPSC-to-iCM differentiation and its relation to iCM fate. We found that DTU is consistently displayed by a subset of genes during iCM differentiation. DTU largely operates on a distinct set of genes than DGE, and both impact different biological processes. The DTU is used more often by protein coding in the late stage of iCM differentiation. The DTU-displaying genes are linked with functions specific to CMs, including ion signaling and cell junction organization, and their expression is cell-type specific. The RNA binding proteins (RBPs) involved in shaping the alternative splicing during the iCM differentiation experience early directed gene expression changes in their expression. Our research emphasizes that analyzing transcript variant expression levels is crucial for uncovering novel genes and functions, and for mapping fine-tuning gene expression and cardiomyocyte-specific functions during cell differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274653 | GEO | 2024/08/18

REPOSITORIES: GEO

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Project description:Hoppe2012 - Predicting changes in metabolic function using transcript profiles Measuring metabolite concentrations, reaction fluxes, and enzyme activities on large scale are tricky tasks in the study of cellular metabolism. Here, a method that predicts activity changes of metabolic functions based on relative transcript profiles, has been presented. It provides a ranked list of most regulated functions. The method has been applied to TGF-beta treatment of hepatocyte cultures. This stoichiometric model of the mouse hepatocyte is based on a corrected and extended version of HepatoNet1. This model is described in the article: ModeScore: A Method to Infer Changed Activity of Metabolic Function from Transcript Profiles Andreas Hoppe and Hermann-Georg Holzhütter German Conference on Bioinformatics 2012; Publ.13.09.2012 Abstract: Genome-wide transcript profiles are often the only available quantitative data for a particular perturbation of a cellular system and their interpretation with respect to the metabolism is a major challenge in systems biology, especially beyond on/off distinction of genes. We present a method that predicts activity changes of metabolic functions by scoring reference flux distributions based on relative transcript profiles, providing a ranked list of most regulated functions. Then, for each metabolic function, the involved genes are ranked upon how much they represent a specific regulation pattern. Compared with the naïve pathway-based approach, the reference modes can be chosen freely, and they represent full metabolic functions, thus, directly provide testable hypotheses for the metabolic study. In conclusion, the novel method provides promising functions for subsequent experimental elucidation together with outstanding associated genes, solely based on transcript profiles. This model is hosted on BioModels Database and identified by: MODEL1208060000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. PMID: 20587024 . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to [CC0 Public Domain Dedication>http://creativecommons.org/publicdomain/zero/1.0/] for more information.

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Exploring the Dynamics and Consequences of Differential Transcript Usage in Cardiomyocyte Fate Specification

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