Published October 13, 2023 | Version v1
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Transcriptional Variabilities in Human hiPSC-derived Cardiomyocytes: All Genes Are Not Equal and Their Robustness May Foretell Donor's Disease Susceptibility

Description

We characterized transcriptional variability from a hiPSC-derived cardiomyocyte (hiPSC-CM) study of left ventricular hypertrophy (LVH) using donor samples from the HyperGEN study. Multiple hiPSC-CM cell lines were used to assess variabilities from reprogramming, differentiation, and donors. Variability arising from pathological alterations was assessed using a cardiac stimulant applied to the hiPSC-CMs to trigger hypertrophic responses. We found that for most genes (73.3%~85.5%), technical variability was smaller than biological variability. Further, we identified and characterized lists of "noise" genes showing greater technical variability and "signal" genes showing greater biological variability. Together, they support a "genetic robustness" hypothesis of disease-modeling whereby cellular response to relevant stimuli in hiPSC-derived somatic cells from diseased donors tends to show more transcriptional variability. Our findings suggest that hiPSC-CMs can provide a valid model for cardiac hypertrophy and distinguish between technical and disease-relevant transcriptional changes.

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Additional details

Funding

National Institutes of Health
Functional GWAS for LVH using iPS-derived Cardiomyocytes: The HyperGEN ciPS Stud 5U01HL107437-05

Dates

Submitted
2023-10-13
Deposit to Zenodo