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Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis

Dissecting the gene expression programs which control the early stage cardiovascular development is essential for understanding the molecular mechanisms of human heart development and heart disease. Here, we performed transcriptome sequencing (RNA-seq) of highly purified human Embryonic Stem Cells (...

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Autores principales: Li, Yang, Lin, Bo, Yang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440522/
https://www.ncbi.nlm.nih.gov/pubmed/25997157
http://dx.doi.org/10.1038/srep09758
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author Li, Yang
Lin, Bo
Yang, Lei
author_facet Li, Yang
Lin, Bo
Yang, Lei
author_sort Li, Yang
collection PubMed
description Dissecting the gene expression programs which control the early stage cardiovascular development is essential for understanding the molecular mechanisms of human heart development and heart disease. Here, we performed transcriptome sequencing (RNA-seq) of highly purified human Embryonic Stem Cells (hESCs), hESC-derived Multipotential Cardiovascular Progenitors (MCPs) and MCP-specified three cardiovascular lineages. A novel algorithm, named as Gene Expression Pattern Analyzer (GEPA), was developed to obtain a refined lineage-specificity map of all sequenced genes, which reveals dynamic changes of transcriptional factor networks underlying early human cardiovascular development. Moreover, our GEPA predictions captured ~90% of top-ranked regulatory cardiac genes that were previously predicted based on chromatin signature changes in hESCs, and further defined their cardiovascular lineage-specificities, indicating that our multi-fate comparison analysis could predict novel regulatory genes. Furthermore, GEPA analysis revealed the MCP-specific expressions of genes in ephrin signaling pathway, positive role of which in cardiomyocyte differentiation was further validated experimentally. By using RNA-seq plus GEPA workflow, we also identified stage-specific RNA splicing switch and lineage-enriched long non-coding RNAs during human cardiovascular differentiation. Overall, our study utilized multi-cell-fate transcriptomic comparison analysis to establish a lineage-specific gene expression map for predicting and validating novel regulatory mechanisms underlying early human cardiovascular development.
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spelling pubmed-44405222015-05-29 Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis Li, Yang Lin, Bo Yang, Lei Sci Rep Article Dissecting the gene expression programs which control the early stage cardiovascular development is essential for understanding the molecular mechanisms of human heart development and heart disease. Here, we performed transcriptome sequencing (RNA-seq) of highly purified human Embryonic Stem Cells (hESCs), hESC-derived Multipotential Cardiovascular Progenitors (MCPs) and MCP-specified three cardiovascular lineages. A novel algorithm, named as Gene Expression Pattern Analyzer (GEPA), was developed to obtain a refined lineage-specificity map of all sequenced genes, which reveals dynamic changes of transcriptional factor networks underlying early human cardiovascular development. Moreover, our GEPA predictions captured ~90% of top-ranked regulatory cardiac genes that were previously predicted based on chromatin signature changes in hESCs, and further defined their cardiovascular lineage-specificities, indicating that our multi-fate comparison analysis could predict novel regulatory genes. Furthermore, GEPA analysis revealed the MCP-specific expressions of genes in ephrin signaling pathway, positive role of which in cardiomyocyte differentiation was further validated experimentally. By using RNA-seq plus GEPA workflow, we also identified stage-specific RNA splicing switch and lineage-enriched long non-coding RNAs during human cardiovascular differentiation. Overall, our study utilized multi-cell-fate transcriptomic comparison analysis to establish a lineage-specific gene expression map for predicting and validating novel regulatory mechanisms underlying early human cardiovascular development. Nature Publishing Group 2015-05-21 /pmc/articles/PMC4440522/ /pubmed/25997157 http://dx.doi.org/10.1038/srep09758 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Yang
Lin, Bo
Yang, Lei
Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title_full Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title_fullStr Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title_full_unstemmed Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title_short Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis
title_sort comparative transcriptomic analysis of multiple cardiovascular fates from embryonic stem cells predicts novel regulators in human cardiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440522/
https://www.ncbi.nlm.nih.gov/pubmed/25997157
http://dx.doi.org/10.1038/srep09758
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