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Series GSE126458 Query DataSets for GSE126458
Status Public on Feb 13, 2019
Title Gene expression and chromatin organization changes in lamin A/C haploinsufficient human induced pluripotent stem cell-derived cardiomyocytes [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Pathogenic mutations in A-type nuclear lamins may dysregulate gene expression due to changes in chromatin organization into active (A) and inactive (B) compartments. To test this, we performed genome-wide chromosome conformation analyses (Hi-C) and transcriptome profiling (RNA-seq) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a haploinsufficient mutation for Lamin A/C that causes cardiac laminopathy. Mutant hiPSC-CM have marked electrophysiological, contractile, and gene expression alterations. While large-scale changes in chromatin topology are evident, differences in chromatin compartmentalization are limited to a few hotspots. These regions normally transition from A to B during cardiogenesis, but remain in A in mutant hiPSC-CM. Non-cardiac genes located within such aberrant domains are ectopically expressed, including the neuronal P/Q-type calcium channel CACNA1A. Pharmacological inhibition of the resulting currents partially mitigates elongation of field potential duration in mutant hiPSC-CM. On the other hand, A/B compartment changes do not explain most gene expression alterations observed in mutant hiPSC-CM, putting in perspective the role of chromatin organization dysregulation in cardiac laminopathy.
 
Overall design RNA-seq analyses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a heterozygous R225X mutation (mutant), and hiPSC-CM from two isogenic control lines where such mutation was reverted to the wild-type allele using CRISPR/Cas9 (corrected); three biological replicates from independent differentiations per cell line.
 
Contributor(s) Bertero A, Murry CE
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Submission date Feb 12, 2019
Last update date Mar 26, 2019
Contact name Alessandro Bertero
E-mail(s) abertero@uw.edu
Organization name University of Washington
Department Institute for Stem Cell and Regenerative Medicine
Street address 850 Republican St
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (9)
GSM3602079 RNA-seq library corrected 1 rep 1
GSM3602080 RNA-seq library corrected 1 rep 2
GSM3602081 RNA-seq library corrected 1 rep 3
This SubSeries is part of SuperSeries:
GSE126460 Gene expression and chromatin organization changes in lamin A/C haploinsufficient human induced pluripotent stem cell-derived cardiomyocytes
Relations
BioProject PRJNA521977
SRA SRP185716

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
GSE126458_gene_exp.diff.gz 2.2 Mb (ftp)(http) DIFF
GSE126458_genes.fpkm_table.txt.gz 602.3 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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