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Data for 3D Organoid Model Assessment of Influence of Chemicals on Morphogenetic Fusion.

Metadata Updated: November 12, 2020

Organogenesis in the embryo involves cell differentiation and organization events that are unique to each tissue and organ and are susceptible to developmental toxicants. Animal models are the gold standard for identifying putative teratogens, but the limited throughput of developmental toxicological studies in animals coupled with the limited concordance between animal and human teratogenicity motivates a different approach. In vitro organoid models can mimic the cellular architecture and phenotype of many tissues and organs, and the three-dimensional (3D) architecture of organoids presents an opportunity to study developmental human toxicology. Common themes during development like the involvement of epithelial-mesenchymal transition and tissue fusion present an opportunity to develop in vitro models to study cell and tissue morphogenesis. We previously described organoids composed of human stem and progenitor cells that recapitulated the cellular features of palate fusion, and here we further characterized the model by examining pharmacological inhibitors targeting known palatogenesis and epithelial morphogenesis pathways as well as twelve cleft palate teratogens identified from rodent models. Organoid survival was dependent on signaling through EGF, IGF, HGF, and FGF pathways, and organoid fusion was disrupted by inhibition of BMP signaling. We observed concordance between the effects of EGF, FGF, and BMP inhibitors on organoid fusion and epithelial cell migration in vitro, suggesting that organoid fusion is dependent on epithelial morphogenesis. Three of the twelve putative cleft palate teratogens studied here significantly disrupted in vitro fusion, including theophylline, triamcinolone, and valproic acid. Tributyltin chloride and all-trans retinoic acid (ATRA) were cytotoxic to fusing organoids. The study herein demonstrates the utility of the in vitro fusion assay for identifying chemicals that disrupt human organoid survival and morphogenesis in a scalable format amenable to toxicology screening.

This dataset is associated with the following publication: Belair, D., C. Wolf, S. Moorefield, C. Wood, C. Becker, and B. Abbott. A Three-Dimensional Organoid Culture Model to Assess the Influence of Chemicals on Morphogenetic Fusion.. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 394-408, (2018).

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Public: This dataset is intended for public access and use. License: See this page for license information.

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Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020
Publisher U.S. EPA Office of Research and Development (ORD)
Data Last Modified 2018-04-10
Public Access Level public
Bureau Code 020:00
Schema Version
Harvest Object Id 7ec3011f-f3ec-4869-afa4-1e41517b3a80
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
Program Code 020:000
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents
Source Datajson Identifier True
Source Hash 0c0af18b2bae05a8fafdfc8cc2ae1937916f26d9
Source Schema Version 1.1

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