Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach

Abstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart fai...

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Autores principales:	Momoko Hamano, Seitaro Nomura, Midori Iida, Issei Komuro, Yoshihiro Yamanishi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a8044467d1be4acda25dd41642b4d56d
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spelling	oai:doaj.org-article:a8044467d1be4acda25dd41642b4d56d2021-12-02T14:26:12ZPrediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach10.1038/s41598-021-86821-y2045-2322https://doaj.org/article/a8044467d1be4acda25dd41642b4d56d2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86821-yhttps://doaj.org/toc/2045-2322Abstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure.Momoko HamanoSeitaro NomuraMidori IidaIssei KomuroYoshihiro YamanishiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
description	Abstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure.
format	article
author	Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi
author_facet	Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi
author_sort	Momoko Hamano
title	Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
title_short	Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
title_full	Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
title_fullStr	Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
title_full_unstemmed	Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
title_sort	prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a8044467d1be4acda25dd41642b4d56d
work_keys_str_mv	AT momokohamano predictionofsinglecellmechanismsfordiseaseprogressioninhypertrophicremodellingbyatransomicsapproach AT seitaronomura predictionofsinglecellmechanismsfordiseaseprogressioninhypertrophicremodellingbyatransomicsapproach AT midoriiida predictionofsinglecellmechanismsfordiseaseprogressioninhypertrophicremodellingbyatransomicsapproach AT isseikomuro predictionofsinglecellmechanismsfordiseaseprogressioninhypertrophicremodellingbyatransomicsapproach AT yoshihiroyamanishi predictionofsinglecellmechanismsfordiseaseprogressioninhypertrophicremodellingbyatransomicsapproach
_version_	1718391388151742464

Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach

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