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Series GSE126401 Query DataSets for GSE126401
Status Public on May 02, 2019
Title Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate [Isl1_RNA_seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and woks in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment.
Overall design Nkx2.5GFP reporter ES cell line stably transfected with Isl1Sh constructs were generated. Isl1Knockdown ES cell lines were differentiated into cardiovascular progenitors. Genomewide RNA-seq profiles were generated.
Contributor(s) Cordero J, Gao R, Dobreva G
Citation(s) 31024170
Submission date Feb 11, 2019
Last update date Jul 22, 2019
Contact name Gergana Dobreva
Organization name Medical Faculty Mannheim/University of Heidelberg
Department Cardiovascular Genomics and Epigenomics
Lab AG Dobreva
Street address Ludolf-Krehl-Str. 7-11
City Mannheim
State/province Baden W├╝rttemberg
ZIP/Postal code 68167
Country Germany
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (4)
GSM3597786 Day5_CPC_Isl1_control_RNA_seq_rep1
GSM3597787 Day5_CPC_Isl1_control_RNA_seq_rep2
GSM3597788 Day5_CPC_Isl1_KO_RNA_seq_rep1
This SubSeries is part of SuperSeries:
GSE80383 Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate
BioProject PRJNA521774
SRA SRP185544

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Supplementary file Size Download File type/resource 41.4 Mb (ftp)(http) BW 36.7 Mb (ftp)(http) BW
GSE126401_Day5_CPC_Isl1_quanty_transcripts_diff_expr.txt.gz 1.9 Mb (ftp)(http) TXT
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Processed data are available on Series record

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