Transcriptomic entropy quantifies cardiomyocyte maturation at single cell level

BioRxiv : the Preprint Server for Biology
S. KannanChulan Kwon

Abstract

While pluripotent stem cell-derived cardiomyocytes (PSC-CMs) offer tremendous potential for a range of clinical applications, their use has been constrained by the failure to mature these cells to a fully adult-like phenotype. Extensive efforts are currently underway with the goal to mature PSC-CMs. However, comprehensive metrics to benchmark the maturation status and trajectory of PSC-CMs have not been established. Here, we developed a novel approach to quantify CM maturation through single cell transcriptomic entropy. We found that transcriptomic entropy is robust across datasets regardless of differences in isolation protocols, library preparation methods, and other potential batch effects. We analyzed over 40 single cell RNA-sequencing (scRNA-seq) datasets and over 45,000 CMs to establish a cross-study, cross-species reference of CM maturation based on transcriptomic entropy. We subsequently computed the maturation status of PSC-CMs by direct comparison to in vivo development. Our study presents a robust, interpretable, and easy-to-use metric for quantifying CM maturation.

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