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Trophinin mediates homophilic and apical cell adhesion between trophoblastic cells and endometrial epithelial cells, which is potentially the initial attachment step in human embryo implantation. Since trophinin is an atypical membrane protein without the signal sequence, it is possible that trophinin localizes to the cytoplasm. By treating trophinin-expressing trophoblastic cells with a series of detergents, we found significant levels of endogenous trophinin in the cytoplasm, particularly at the nuclear envelope (NE). Fluorescence photobleaching of GFP-trophinin expressed in COS-1 cells showed the stable association of trophinin with the NE, suggesting an additional role of trophinin besides apical cell adhesion.

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Clinical translation of stem cell therapies for heart disease requires electrical integration of transplanted cardiomyocytes. Generation of electrically matured human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) is critical for electrical integration. Here, we found that hiPSC-derived endothelial cells (hiPSC-ECs) promoted the expression of selected maturation markers in hiPSC-CMs. Using tissue-embedded stretchable mesh nanoelectronics, we achieved a long-term stable map of human three-dimensional (3D) cardiac microtissue electrical activity. The results revealed that hiPSC-ECs accelerated the electrical maturation of hiPSC-CMs in 3D cardiac microtissues. Machine learning–based pseudotime trajectory inference of cardiomyocyte electrical signals further revealed the electrical phenotypic transition path during development. Guided by the electrical recording data, single-cell RNA sequencing identified that hiPSC-ECs promoted cardiomyocyte subpopulations with a more mature phenotype, and multiple ligand-receptor interactions were up-regulated between hiPSC-ECs and hiPSC-CMs, revealing a coordinated multifactorial mechanism of hiPSC-CM electrical maturation. Collectively, these findings show that hiPSC-ECs drive hiPSC-CM electrical maturation via multiple intercellular pathways.