Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Human iPSC-derived cardiomyocytes of peripartum cardiomyopathy patients reveal aberrant expression of sterol and lipid metabolism pathways

ABSTRACT: To identify the consequences of mechanical stress of differentiated cardiac muscles from healthy- and PPCM individuals. RNA-sequencing data was obtained from 4 individuals from 2 families. Each family had one member with PPCM and one healthy. Individual 1 and 2 were sisters, one healthy, one with PPCM. Individual 3 and 4 were a healthy mother and PPCM daughter. From each patient 4, 6, 1 and 3 clones were derived, respectively. From each clone multiple pairs of cells were collected and either stretched or left static to a total of 40 pairs, with 2 unpaired static samples.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Nils Bomer

PROVIDER: E-MTAB-9053 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Engineered cardiac tissues (ECTs) are platforms to investigate cardiomyocyte maturation and functional integration, to evaluate the feasibility of generating implantable tissues for cardiac repair and regeneration, and may be useful models for pharmacology and toxicology bioassays. These ECTs rapidly mature in vitro to acquire the features of functional cardiac muscle and respond to mechanical load with increased proliferation and maturation. ECTs can be generated from various immature cardiac cell sources and little is known regarding the broad changes in regulatory transcript expression that occur in these in vitro tissues during normal maturation and in response to mechanical or pharmacologic interventions. We tested the hypothesis that global ECT gene expression patterns are sensitive to mechanical loading conditions and tyrosine kinase inhibitors, similar to the maturing myocardium. We generated 3D ECTs from day 14.5 rat embryo ventricular cells, as previously published, and then treated constructs after 5 days in culture for 48 hours with mechanical stretch (5%, 0.5 Hz) and/or the p38MAPK (p38 mitogen-activated protein kinase) selective inhibitor BIRB796. RNA was isolated from 3 sets of experiments and assayed using a standard Agilent rat 4x44k V3 microarray and Pathway Analysis software for transcript expression fold changes and changes in regulatory molecules and networks. At the threshold of a 1.5 fold change in expression, mechanical stretch altered 1,559 transcripts, versus 1,411 for BIRB796, and 1,846 for stretch plus BIRB796. As anticipated, top pathways altered in response to these stimuli include Cellular Development, Cellular Growth and Proliferation; Tissue Development; Cell Death, Cell Signaling, and Small Molecule Biochemistry as well as numerous other pathways. Changes in transcript expression were confirmed by quantitative-PCR for selected regulatory molecules. Thus, ECTs display a broad spectrum of altered gene expression in response to mechanical load and/or tyrosine kinase inhibition, reflecting the complex regulation of proliferation, differentiation, and architectural alignment that occurs during ECT maturation and adaptation. This approach can now be used to test the role of individual molecules and pathways on the regulation of ECT maturation and remodeling. 7 and 4 biological replicates with four groups (control, mechanical stretch, BIRB and mechanical stretch with BIRB)

Dataset Information

Human iPSC-derived cardiomyocytes of peripartum cardiomyopathy patients reveal aberrant expression of sterol and lipid metabolism pathways

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets