Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.

<h4>Background</h4>Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibri...

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Autores principales:	Peter C Kahr, Ilaria Piccini, Larissa Fabritz, Boris Greber, Hans Schöler, Hans H Scheld, Andreas Hoffmeier, Nigel A Brown, Paulus Kirchhof
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f74f611bba404314a1e1f5db69086b99
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spelling	oai:doaj.org-article:f74f611bba404314a1e1f5db69086b992021-11-18T07:36:07ZSystematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.1932-620310.1371/journal.pone.0026389https://doaj.org/article/f74f611bba404314a1e1f5db69086b992011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22039477/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria.<h4>Methods</h4>We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery.<h4>Results</h4>We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFβ family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c(+/-) atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c.<h4>Conclusions</h4>Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining "leftness" in the atrium in adult murine and human hearts.Peter C KahrIlaria PicciniLarissa FabritzBoris GreberHans SchölerHans H ScheldAndreas HoffmeierNigel A BrownPaulus KirchhofPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26389 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peter C Kahr Ilaria Piccini Larissa Fabritz Boris Greber Hans Schöler Hans H Scheld Andreas Hoffmeier Nigel A Brown Paulus Kirchhof Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
description	<h4>Background</h4>Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria.<h4>Methods</h4>We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery.<h4>Results</h4>We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFβ family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c(+/-) atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c.<h4>Conclusions</h4>Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining "leftness" in the atrium in adult murine and human hearts.
format	article
author	Peter C Kahr Ilaria Piccini Larissa Fabritz Boris Greber Hans Schöler Hans H Scheld Andreas Hoffmeier Nigel A Brown Paulus Kirchhof
author_facet	Peter C Kahr Ilaria Piccini Larissa Fabritz Boris Greber Hans Schöler Hans H Scheld Andreas Hoffmeier Nigel A Brown Paulus Kirchhof
author_sort	Peter C Kahr
title	Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
title_short	Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
title_full	Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
title_fullStr	Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
title_full_unstemmed	Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
title_sort	systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f74f611bba404314a1e1f5db69086b99
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Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue.

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