@article{d06766039c6f49e185b2b6b29c3c1ffb,
title = "Capturing Cardiogenesis in Gastruloids",
abstract = "Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here, we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo fundamental steps of early heart organogenesis with an in-vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids (gastruloids) mimic embryonic development and support the generation of cardiovascular progenitors, including first and second heart fields. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a putative primitive gut-like tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.",
keywords = "3D cardiac tissue, cardiac organoid, cardiogenesis, development, embryonic organoids, heart, in vitro organogenesis",
author = "Giuliana Rossi and Nicolas Broguiere and Matthew Miyamoto and Andrea Boni and Romain Guiet and Mehmet Girgin and Kelly, {Robert G.} and Chulan Kwon and Lutolf, {Matthias P.}",
note = "Funding Information: We thank Alfonso Martinez Arias for great support throughout the project. We thank Denis Duboule and Nadia Mercader for useful feedback on the manuscript. We thank Gioele La Manno for helpful discussion on single-cell RNA-seq. We thank members of the Lutolf laboratory for discussions and sharing materials, C?dric Blanpain (ULB) for providing Mesp1-GFP cells, Alexander Medvinsky (MRC Edinburgh) for providing Flk1-GFP cells, Andrew Oates (EPFL) and Peter Strnad (Viventis Microscopy S?rl) for making light-sheet LS1 Live microscope available and for technical support, Olivier Burri for EasyXT development, Thierry Laroche for support with Z1 light-sheet imaging, Arne Seitz and other members of Bioimaging and Optics Facility (EPFL) for microscopy support, Jessica Sordet-Dessimoz and Gian-Filippo Mancini from Histology Core Facility for RNAscope, and all personnel of Histology Core Facility, Flow Cytometry Core Facility, and Gene Expression Core Facility (EPFL) for their technical support. This work was funded by EPFL. G.R. and M.P.L. conceived the study, designed experiments, analyzed data, and wrote the manuscript. G.R. performed the experiments, N.B. performed scRNA-seq data analysis, M.M. contributed to experiments with the Hcn4-GFP::Tbx1Cre-RFP mESC line, A.B. performed in vivo light-sheet imaging of Mesp1-GFP and Flk1-GFP gastruloids, R.G. developed the script for the analysis of cardiac structures, M.G. contributed to protocol optimization and data analysis, and C.K. and R.G.K. contributed to study design and data discussion and provided feedback on the manuscript. A.B. is part of Viventis Microscopy S?rl that has commercialized the LS1 light-sheet microscope used in this study for time-lapse imaging of gastruloids. The EPFL (with Cambridge Enterprise Limited) has filed for patent protection (PCT/GB2019/052668) on the embryoid technology described herein, and M.P.L. and G.R. are named as inventors on the patent. Funding Information: We thank Alfonso Martinez Arias for great support throughout the project. We thank Denis Duboule and Nadia Mercader for useful feedback on the manuscript. We thank Gioele La Manno for helpful discussion on single-cell RNA-seq. We thank members of the Lutolf laboratory for discussions and sharing materials, C{\'e}dric Blanpain (ULB) for providing Mesp1-GFP cells, Alexander Medvinsky (MRC Edinburgh) for providing Flk1-GFP cells, Andrew Oates (EPFL) and Peter Strnad (Viventis Microscopy S{\`a}rl) for making light-sheet LS1 Live microscope available and for technical support, Olivier Burri for EasyXT development, Thierry Laroche for support with Z1 light-sheet imaging, Arne Seitz and other members of Bioimaging and Optics Facility (EPFL) for microscopy support, Jessica Sordet-Dessimoz and Gian-Filippo Mancini from Histology Core Facility for RNAscope, and all personnel of Histology Core Facility, Flow Cytometry Core Facility, and Gene Expression Core Facility (EPFL) for their technical support. This work was funded by EPFL . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = feb,
day = "4",
doi = "10.1016/j.stem.2020.10.013",
language = "English (US)",
volume = "28",
pages = "230--240.e6",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}