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Series GSE178751 Query DataSets for GSE178751
Status Public on Dec 01, 2023
Title Distinct epicardial gene regulatory programmes drive development and regeneration of the zebrafish heart
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Unlike the adult mammalian heart, which has limited regenerative capacity, the zebrafish heart can fully regenerate following injury. Reactivation of cardiac developmental programmes is considered key to successfully regenerating the heart, yet the regulatory elements underlying the response triggered upon injury and during development remain elusive. Organ-wide activation of the epicardium is essential for zebrafish heart regeneration and is considered a potential regenerative source to target in the mammalian heart. Here we compared the transcriptome and epigenome of the developing and regenerating zebrafish epicardium by integrating gene expression profiles with open chromatin ATAC-seq data. We identified epicardial enhancer elements with specific activity during development or during adult heart regeneration. By generating gene regulatory networks associated with epicardial development and regeneration, we inferred genetic programmes driving each of these processes, which were largely distinct. We identified Wt1a, Wt1b, and the AP-1 subunits Junbb, Fosab and Fosb as central regulators of the developing network, whereas Hif1ab, Nrf1, Tbx2b and Zbtb7a featured as putative central regulators of the regenerating epicardial network. Targeting hif1ab, nrf1, tbx2b and zbtb7a using CRISPR/Cas9 in injured hearts resulted in elevated epicardial cell numbers infiltrating the wound and excess fibrosis after cryoinjury, illustrating the functional importance of these regulatory factors during zebrafish heart regeneration. Our work reveals striking differences between the regulatory blueprint deployed during epicardial development and regeneration. These findings underline that heart regeneration goes beyond the reactivation of developmental programmes and provide important insights into epicardial regulation.
 
Overall design Bulk ATAC and RNA sequencing of purified zebrafish epicardial cells, either at 5 days-post-fertilization or at 3 days-post-cryoinjury or at 3 days-post-sham
 
Contributor(s) Weinberger M, Simoes FC, Gungoosingh T, Sauka-Spengler T, Riley PR
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Submission date Jun 23, 2021
Last update date Dec 01, 2023
Contact name Paul Richard Riley
E-mail(s) paul.riley@idrm.ox.ac.uk
Organization name University of Oxford
Street address IMS-Tetsuya Nakamura Building, Old Road Campus
City Oxford
ZIP/Postal code OX3 7TY
Country United Kingdom
 
Platforms (1)
GPL20828 Illumina NextSeq 500 (Danio rerio)
Samples (25)
GSM5396895 ATAC-tbx18-control-1
GSM5396896 ATAC-tbx18-control-2
GSM5396897 ATAC-tbx18-larval-1
Relations
BioProject PRJNA740283
SRA SRP325322

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE178751_ATAC_seq_tcf21_larval_vs_adult_count_table.txt.gz 5.0 Mb (ftp)(http) TXT
GSE178751_ATAC_seq_tcf21_larval_vs_adult_peak_annotation.txt.gz 2.0 Mb (ftp)(http) TXT
GSE178751_RNA_seq_tcf21_larval_vs_adult_count_table.txt.gz 674.2 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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