02320nas a2200421   4500000000100000000000100001008004100002260001500043653002700058653002600085653002200111653001900133653001500152100001800167700001800185700001800203700001300221700001700234700002300251700001900274700002800293700002000321700001700341700002600358700001700384700002300401700001600424700001700440700001300457700001400470700001800484245010600502856005500608300000900663490000700672520120500679022001401884       2023                            d  c2023-12-1210aBiomedical Engineering10aDevelopmental biology10aHeart development10aRNA sequencing10aStem cells1 aBrett Volmert1 aArtem Kiselev1 aAniwat Juhong1 aFei Wang1 aAshlin Riggs1 aAleksandra Kostina1 aColin O’Hern1 aPriyadharshni Muniyandi1 aAaron Wasserman1 aAmanda Huang1 aYonatan Lewis-Israeli1 aVishal Panda1 aSudin Bhattacharya1 aAdam Lauver1 aSangbum Park1 aZhen Qiu1 aChao Zhou1 aAitor Aguirre00aA patterned human primitive heart organoid model generated by pluripotent stem cell self-organization  uhttps://www.nature.com/articles/s41467-023-43999-1  a82450 v143 aPluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage primitive heart. Moreover, we provide proof-of-concept demonstration of the value of this system for disease modeling by exploring the effects of ondansetron, a drug administered to pregnant women and associated with congenital heart defects. These findings constitute a significant technical advance for synthetic heart development and provide a powerful tool for cardiac disease modeling.  a2041-1723