Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Activation of Nkx2.5 Transcriptional Program is Required for Adult Myocardial Repair

ABSTRACT: We show that cardiac-specific RNA-sequencing studies reveal a disrupted embryonic Nkx2.5 transcriptional profile despite histologically normal, Nkx2.5 loss-of-function adult myocardium. Yet, adult nkx2.5-/- fish exhibit an impaired ability to recover following ventricular apex amputation as illustrated by retention of fibrin and collagen in the injured area. Complex network analyses illuminate that Nkx2.5 is required to mount a proliferative response for cardiomyocyte renewal and to provoke proteolytic pathways necessary for sarcomere disassembly. Moreover, direct Nkx2.5 targets embedded in these distinct gene regulatory modules coordinate appropriate, multi-faceted injury responses. Altogether, our findings support a previously unrecognized, Nkx2.5-dependent regenerative circuit that invokes myocardial proliferation and dedifferentiation to ensure effective regeneration in the teleost heart.

ORGANISM(S): Danio rerio

PROVIDER: GSE164966 | GEO | 2022/04/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nkx2.5 regulates Jarid2 during outflow tract morphogenesis

Project description:The transcription factor Nkx2.5 is required for specification of pharyngeal arch second heart field (SHF) progenitors that contribute to outflow tract (OFT) and right ventricle (RV) formation. Multiple sets of microarray data were analyzed to identify genes that are candidate targets of Nkx2.5 in the second heart field. These sets are: 1) publicly available data for cardiothoracic tissue from E9.5 Nkx2.5 wild-type, heterozygous and homozygous embryos; 2) an analysis of mouse E10.5 pharyngeal arch tissue; 3) an analysis of mouse E12.5 heart tissue; and 4) a temporal analysis of the cardiogenic cell line P19CL6. This combined analysis identified 11 genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF-containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5 expression. This SuperSeries is composed of the SubSeries listed below.

2010-05-17 | GSE17936 | GEO

Nkx2.5 regulates Jarid2 during outflow tract morphogenesis

2010-05-17 | E-GEOD-17936 | biostudies-arrayexpress

Nr2f1a maintains atrial nkx2.5 expression to repress pacemaker identity within venous atrial cardiomyocytes of zebrafish

Project description:Maintenance of cardiomyocyte identity is vital for normal heart development and function. However, our understanding of cardiomyocyte plasticity remains incomplete. Here, we show that sustained expression of the zebrafish transcription factor Nr2f1a prevents the progressive acquisition of ventricular cardiomyocyte (VC) and pacemaker cardiomyocyte (PC) identities within distinct regions of the atrium. Transcriptomic analysis of flow-sorted atrial cardiomyocytes (ACs) from nr2f1a mutant zebrafish embryos showed increased VC marker gene expression and altered expression of core PC regulatory genes, including decreased expression of nkx2.5, a critical repressor of PC differentiation. At the arterial (outflow) pole of the atrium in nr2f1a mutants, cardiomyocytes resolve to VC identity within the expanded atrioventricular canal. However, at the venous (inflow) pole of the atrium, there is a progressive wave of AC transdifferentiation into PCs across the atrium toward the arterial pole. Restoring Nkx2.5 is sufficient to repress PC marker identity in nr2f1a mutant atria and analysis of chromatin accessibility identified a Nr2f1a-dependent nkx2.5 enhancer expressed in the atrial myocardium directly adjacent to PCs. CRISPR/Cas9-mediated deletion of the putative nkx2.5 enhancer leads to a loss of Nkx2.5-expressing ACs and expansion of a PC reporter, supporting that Nr2f1a limits PC differentiation within venous ACs via maintaining nkx2.5 expression. The Nr2f-dependent maintenance of AC identity within discrete atrial compartments may provide insights into the molecular etiology of concurrent structural congenital heart defects and associated arrhythmias.

2023-05-12 | GSE194054 | GEO

Genomic occupancy of TFs ISL1 and NKX2.5 in cardiac and neural populations

Project description:ChIP-sequencing demonstrated that ISL1 binds cardiac DNA in a cell-type-specific manner, and that NKX2.5 is both necessary and sufficient for this localization.

2023-10-17 | GSE195474 | GEO

Congenital heart disease in Csx/ Nkx2.5 mutant embryos

Project description:We have developed gene-targeted mice with deletion of Nkx2.5. Embryos were isolated at embryonic day 9.5 and the middle third containing the heart was run on Affymetrix Mu11kA and Mu11kB arrays. For more information about this model see http://cardiogenomics.med.harvard.edu/groups/proj1/pages/csx_home.html Keywords = Congenital heart disease Keywords: other

2002-08-02 | GSE78 | GEO

Transcription profiling of hearts from Nkx2.5 knockout mice (mouse model of congenital heart disease) at embryonic day 12.5 shows Nkx2.5 is not only crucial during early steps of cardiogenesis but also plays an important role at later developmental stages

Project description:The NK2 family of homeobox genes constitutes a family of transcription factors that play an important role in different developmental processes. Members of this group are characterized by two highly conserved protein domains: the homeodomain, conferring DNA binding activity, and the NK2-specific domain (NK2-SD) of yet unknown function. One of the best characterized members of this group is the early cardiogenic marker Nkx2.5. Loss of function of Nkx2.5 leads to embryonic lethality around E10.5 due to an arrest of heart development at the looping stage. We have further dissected the function of Nkx2.5 in vivo by creating a knockout mouse line harboring an in frame deletion of the NK2-SD by Cre/loxP mediated excision. Homozygous mutant mice die at E14.5 due to severe cardiac malformations, e.g. common AV canal, DORV, and VSD. Lack of the NK2-SD leads to downregulation of the ventricular markers MLC-2v and Irx4 specifically in the right ventricle, and is accompanied with reduced right ventricular function. This function of Nkx2.5 seems to be independent of its ability to bind target DNA, since lack of the NK2-SD does not alter the DNA binding activity of Csx/Nkx2.5 in vitro. Heterozygous mutant mice show a spectrum of cardiac defects related to cardiac septation and valve morphogenesis, but lack conduction system defects as reported for heterozygous Nkx2.5 mice. The phenotype observed in NK2-SD mutant mice shows that Nkx2.5 is not only crucial during early steps of cardiogenesis but also plays an important role at later developmental stages. Embryos were isolated at embryonic day 12.5. The entire embryo heart was taken and isolated in ice-cold PBS and immediately frozen on dry-ice. Total RNA was extracted from pooled samples of wildtype, heterozygous and mutant embryos.

2007-12-13 | E-GEOD-528 | biostudies-arrayexpress

Effect of Nkx2.5 mutation on gene expression profiles of mouse embryonic stem cells undergoing cardiac differentiation.

Project description:The purpose of this study was to determine the effect of Nkx2.5 mutation (R141C) on gene expression in mouse embryonic stem cells during their differentiation into cardiac progenitors.

2017-12-31 | GSE83428 | GEO

RNAi knock down in mouse cardiomyocyte cell line HL-1 using siRNAs against Gata4, Mef2a, Nkx2.5 and Srf to identify downstream targets

Project description:HL-1 cells treated with two different siRNAs against Gata4, Mef2a, Nkx2.5 and Srf each in duplicate to identify downstream targets.

2011-01-05 | E-TABM-376 | biostudies-arrayexpress

Chromatin immunoprecipitation to identify binding sites for Gata4, Mef2a, Nkx2.5, Srf, p300, Pol_II, H3ac, H3K4me1 in mouse cardiomyocyte cell line, HL1

Project description:The aim of the experiment was to identify genome wide binding sites for Gata4, Mef2a, Nkx2.5, Srf, p300, Pol_II, H3ac, H3K4me1 by using Chromatin Immunoprecipitation followed by microarray analysis (ChIP-chip) in HL1 cells.

2011-01-05 | E-TABM-378 | biostudies-arrayexpress

Activation of Nkx2.5 Transcriptional Program is Required for Adult Myocardial Repair

Project description:Activation of Nkx2.5 Transcriptional Program is Required for Adult Myocardial Repair

| PRJNA692707 | ENA