TY - JOUR
T1 - A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization
AU - Volmert, Brett
AU - Kiselev, Artem
AU - Juhong, Aniwat
AU - Wang, Fei
AU - Riggs, Ashlin
AU - Kostina, Aleksandra
AU - O’Hern, Colin
AU - Muniyandi, Priyadharshni
AU - Wasserman, Aaron
AU - Huang, Amanda
AU - Lewis-Israeli, Yonatan
AU - Panda, Vishal
AU - Bhattacharya, Sudin
AU - Lauver, Adam
AU - Park, Sangbum
AU - Qiu, Zhen
AU - Zhou, Chao
AU - Aguirre, Aitor
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Pluripotent 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.
AB - Pluripotent 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.
UR - http://www.scopus.com/inward/record.url?scp=85179645516&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-43999-1
DO - 10.1038/s41467-023-43999-1
M3 - Article
C2 - 38086920
AN - SCOPUS:85179645516
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 8245
ER -