TY - JOUR
KW - Biomedical Engineering
KW - Developmental biology
KW - Heart development
KW - RNA sequencing
KW - Stem cells
AU - Brett Volmert
AU - Artem Kiselev
AU - Aniwat Juhong
AU - Fei Wang
AU - Ashlin Riggs
AU - Aleksandra Kostina
AU - Colin O’Hern
AU - Priyadharshni Muniyandi
AU - Aaron Wasserman
AU - Amanda Huang
AU - Yonatan Lewis-Israeli
AU - Vishal Panda
AU - Sudin Bhattacharya
AU - Adam Lauver
AU - Sangbum Park
AU - Zhen Qiu
AU - Chao Zhou
AU - Aitor Aguirre
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.
BT - Nature Communications
DA - 2023-12-12
DO - 10.1038/s41467-023-43999-1
LA - en
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.
PY - 2023
EP - 8245
T2 - Nature Communications
TI - A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization
UR - https://www.nature.com/articles/s41467-023-43999-1
VL - 14
Y2 - 2024-08-13
SN - 2041-1723
ER -