Abstract
Transcriptome landscape of organs from mice and humans offers perspectives on the process of how organs develop and the similarity and diversity in each organ between the species. Among multi-species and multi-organ dataset, which was previously generated, we focused on the mouse and human dataset and performed a reanalysis to provide a more specific perspective on the maturation of human cardiomyocytes. First, we examined how organs diversify their transcriptome during development across and within two species. We unexpectedly identified that ribosomal genes were differentially expressed between mice and humans. Second, we examined the corresponding ages of organs in mice and humans and found that the corresponding developmental ages did not match throughout organs. Mouse hearts at P0–3 and human hearts at 18–19 wpc showed the most proximity in the regard of the transcriptome. Third, we identified a novel set of maturation marker genes that are more consistent between mice and humans. In contrast, conventionally used maturation marker genes only work well with mouse hearts. Finally, we compared human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) in maturation-enhanced conditions to human fetal and adult hearts and revealed that human PSC-CMs only expressed low levels of the potential maturation marker genes. Our findings provide a novel foundation to study cardiomyocyte maturation and highlight the importance of studying human samples rather than relying on a mouse time-series dataset.
Highlights
Understanding the transcriptome landscape of mouse developing hearts provided a compass to navigate how cardiomyocyte mature in vivo and a foundation to determine the maturity of mouse pluripotent stem cell-derived cardiomyocytes (PSC-CMs) cultured in vitro (Uosaki et al, 2015)
Cardiomyocyte maturation arrests at an immature state in vitro, and discovering a new method to generate mature PSC-CMs is a huge point of emphasis for the last decade (Uosaki et al, 2015; Cho et al, 2017; Ronaldson-Bouchard et al, 2018) after efficient differentiation methods were developed (Uosaki et al, 2011; Tohyama et al, 2013; Burridge et al, 2014)
Some studies compared gene expression of PSC-CMs and adult human cardiomyocytes with a selected set of genes (Yang et al, 2014a; Karakikes et al, 2015), the selection of such genes is based on mouse expression profiles and the expression kinetics of the maturation marker genes during human heart development were unknown
Summary
Understanding the transcriptome landscape of mouse developing hearts provided a compass to navigate how cardiomyocyte mature in vivo and a foundation to determine the maturity of mouse pluripotent stem cell-derived cardiomyocytes (PSC-CMs) cultured in vitro (Uosaki et al, 2015). The maturation of cardiomyocytes is a continuous process from early embryo to adult, but the maturation of PSC-CMs arrested at the late-embryonic stage (Uosaki et al, 2015), which demanded more information on cardiomyocyte maturation during postnatal. Due to the limited availability of human heart samples at late-embryos to early ages, only transcriptome datasets of fetal and adult human hearts were evaluated in the past (Kuppusamy et al, 2015; Uosaki and Taguchi, 2016). We reanalyzed the dataset to obtain more accurate information about the transcriptome landscape of mice and humans, especially in hearts from embryonic to adult stage and determined expression kinetics of maturation-related genes in human hearts
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