Summary
Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.
Description
Cardioids reveal self-organizing principles of human cardiogenesis - ScienceDirect
%0 Journal Article
%1 HOFBAUER20213299
%A Hofbauer, Pablo
%A Jahnel, Stefan M.
%A Papai, Nora
%A Giesshammer, Magdalena
%A Deyett, Alison
%A Schmidt, Clara
%A Penc, Mirjam
%A Tavernini, Katherina
%A Grdseloff, Nastasja
%A Meledeth, Christy
%A Ginistrelli, Lavinia Ceci
%A Ctortecka, Claudia
%A Šalic, Šejla
%A Novatchkova, Maria
%A Mendjan, Sasha
%D 2021
%J Cell
%K tiny-hearts
%N 12
%P 3299-3317.e22
%R https://doi.org/10.1016/j.cell.2021.04.034
%T Cardioids reveal self-organizing principles of human cardiogenesis
%U https://www.sciencedirect.com/science/article/pii/S0092867421005377
%V 184
%X Summary
Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.
@article{HOFBAUER20213299,
abstract = {Summary
Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.},
added-at = {2021-07-03T09:44:35.000+0200},
author = {Hofbauer, Pablo and Jahnel, Stefan M. and Papai, Nora and Giesshammer, Magdalena and Deyett, Alison and Schmidt, Clara and Penc, Mirjam and Tavernini, Katherina and Grdseloff, Nastasja and Meledeth, Christy and Ginistrelli, Lavinia Ceci and Ctortecka, Claudia and Šalic, Šejla and Novatchkova, Maria and Mendjan, Sasha},
biburl = {https://www.bibsonomy.org/bibtex/2c7e50e3f3cbd4182208a370ae37ece32/gameovercite},
description = {Cardioids reveal self-organizing principles of human cardiogenesis - ScienceDirect},
doi = {https://doi.org/10.1016/j.cell.2021.04.034},
interhash = {63e619fbb29c8b3aaae0f9f476c9b427},
intrahash = {c7e50e3f3cbd4182208a370ae37ece32},
issn = {0092-8674},
journal = {Cell},
keywords = {tiny-hearts},
number = 12,
pages = {3299-3317.e22},
timestamp = {2021-07-03T09:44:35.000+0200},
title = {Cardioids reveal self-organizing principles of human cardiogenesis},
url = {https://www.sciencedirect.com/science/article/pii/S0092867421005377},
volume = 184,
year = 2021
}