Generation of thyroid and lung organoids from stem cells
AssigneeUniversite Libre de Bruxelles
InventorsSabine, Aline, Nadine COSTAGLIOLA, Mirian ROMITTI
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Abstract
The invention relates to a method for differentiating pluripotent stem cells into thyroid or lung organoids by forming embryoid bodies, differentiating the embryoid bodies into definitive endoderm, inducing (over) expression of NKX2-1 and PAX8, and treatment with respectively, a cyclic monophosphate, a glucocorticoid, thyroid-stimulating hormone and a TGF-β inhibitor, or with a cyclic monophosphate, insulin or IGF-1, and a TGF-β inhibitor. The invention also relates to thyroid and lung organoids obtained by the methods as well as uses thereof for therapeutic applications and medicinal applications such as drug screening or research purposes.
Claims33
A (in vitro) method for generating a thyroid organoid or a lung organoid from human pluripotent stem cells, said method comprising:
- a. generating an embryoid body (EB) from human pluripotent stem cells (hPSCs);
- b. culturing the embryoid body in a 3D matrix under conditions to induce differentiation into definitive endoderm;
- c. transiently overexpressing NKX2-1 and PAX8 in the definitive endoderm to induce differentiation of endodermal cells into thyroid and lung progenitor cells;
- and
- d. culturing the thyroid and lung progenitor cells in the 3D matrix in a differentiation medium for a period of time sufficient to generate a thyroid organoid or a lung organoid.
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