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Follistatin secreted by myocytes from hiPSCs results in cardiomyocyte cytokinesis in large mammal hearts with postinfarction LV remodeling

ABSTRACT: In this work, we generated a new human induced-pluripotent stem cells derived-cardiomyocytes (hiPSC-CM); in this new hiPSC-CM cell line, Cyclin D2 (CCND2), a cell-cycle activator, was overexpressed, and class I-II of major histocompatibility complex were knocked down. This new cell line (named KO/OEhiPSC-CM) and the wildtype hiPSC-CM (name WThiPSC-CM) were transplanted into pig hearts with ischemic-reperfusion (I/R). The objective is to examine engraftment, cardiac function change, and how the host (pig) heart responded to the transplantation. Surprisingly, while the pig hearts receiving KO/OEhiPSC-CM showed significant cardiac function 4 weeks after I/R, the KO/OEhiPSC-CM grafts were undetectable. Analyzing the single-nuclei RNA sequencing (SnRNAseq) data of these pig hearts showed that 1) the host cardiomyocyte actively reentered cell-cycle, which was among the key factors for cardiac function improvement; 2) this effect was mediated via HIPPO/YAP signaling pathway; and 3) HIPPO/YAP signaling pathway activity was a result of Follistatin (FST) secreted by the transplanted KO/OEhiPSC-CM.

ORGANISM(S): Sus scrofa

PROVIDER: GSE279567 | GEO | 2024/12/10

REPOSITORIES: GEO

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