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A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree.

eLife | 2017

Connection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process. Gata6 is expressed in SMCs and its target genes activation control SMC differentiation. Furthermore, Gata6 is sufficient to promote SMCs differentiation in vivo, and drive preservation of aortic arches that ought to regress. These findings identify Gata6-directed differentiation of NC to SMCs as an essential mechanism that specifies the aortic tree, and provide a new framework for how mutations in GATA6 lead to congenital heart disorders in humans.

Pubmed ID: 28952437 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

RRID:SCR_008452

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Cuffdiff (tool)

RRID:SCR_001647

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ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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ArrayExpress (tool)

RRID:SCR_002964

International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.

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PrimerBank (tool)

RRID:SCR_006898

Database of human and mouse primer pairs for gene expression analysis by polymerase chain reaction (PCR) and quantitative PCR (qPCR). A total of 306,800 primers covering most known human and mouse genes can be accessed from the PrimerBank database, together with information on these primers such as T(m), location on the transcript and amplicon size. For each gene, at least one primer pair has been designed and in many cases alternative primer pairs exist. Primers have been designed to work under the same PCR conditions, thus facilitating high-throughput QPCR. All primers in PrimerBank were carefully designed to ensure gene specificity. All experimental validation data for mouse primers are available from PrimerBank. You can submit your primers. They will be added to the database once they are properly QCd.

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Advanced 3D Visualization and Volume Modeling (tool)

RRID:SCR_007353

Software tool for visualizing, manipulating, and understanding data from tomography, microscopy, MRI and other imaging processes.Used to import and export options, to processes 3D image filtering and DTI based fiber tracking to visualization, volume and surface rendering, author tools for virtual reality navigation, video generation, and more.

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Meis1/2 (C-17) (antibody)

RRID:AB_2143020

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RRID:AB_476856

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CD31 (antibody)

RRID:AB_393571

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GATA-6 (D61E4) XP Rabbit mAb (antibody)

RRID:AB_10705521

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Advanced 3D Visualization and Volume Modeling (software resource)

RRID:SCR_014305

Software tool for visualizing, manipulating, and understanding data from tomography, microscopy, MRI and other imaging processes.Used to import and export options, to processes 3D image filtering and DTI based fiber tracking to visualization, volume and surface rendering, author tools for virtual reality navigation, video generation, and more.

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edgeR (software resource)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

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Cufflinks (software resource)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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diffReps (software resource)

RRID:SCR_010873

Finding differential chromatin modification sites from ChIP-seq data.

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HOMER (software resource)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

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GREAT: Genomic Regions Enrichment of Annotations Tool (software resource)

RRID:SCR_005807

Data analysis service that predicts functions of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. The utility of GREAT extends to data generated for transcription-associated factors, open chromatin, localized epigenomic markers and similar functional data sets, and comparative genomics sets. Platform: Online tool

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Trimmomatic (data processing software)

RRID:SCR_011848

Software Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.

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MACS (software resource)

RRID:SCR_013291

Software Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.

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Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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