How insulin shapes lung development in a new human stem cell organoid model
Scope of the method
- Human health
- Basic Research
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
Description
- lung organoids
- insulin
- lung development
- airways organoids
- alveolar organoids
- 3D in vitro model
- glucose metabolism
- idiopathic pulmonary fibrosis
- human embryonic stem cell derived organoid model
- lung airways organoids
- lung alveolar organoids
- hESC-derived organoids
- lung diseases
- insulin metabolic pathways
- diabetes and idiopathic pulmonary fibrosis
Respiratory diseases are one of the leading causes of mortality. Despite the efforts to understand lung development, physiology, and pathology, this field remains in its early stages. In vitro models can replicate lung physiology to comprehend development, function, and pathology. Lung organoids (LOs) are 3D models that emulate the diverse developmental stages of the lung and its 3D architecture and functional characteristics. We adopted an organoid model derived from hESCs with transient overexpression of the lung/thyroid transcription factor NKX2.1. Insulin plays a role in LO generation, and airway, alveolar, and mesenchymal cell types were identified. Transcriptomic analysis reveals insulin's role in enhancing lung progenitors’ differentiation, glycolysis, and PI3K pathway activation. Insulin's indispensability throughout lung development is evident, as its removal at different stages disrupts LO generation and maturation. The protocol adopted is under the International Patent (WO/2023/099526). Our research emphasizes insulin's pivotal role in transforming NKX2.1 endodermal cells into LOs and aims to unveil the intricate dynamics behind it. Finally, this method has been applied to model idiopathic pulmonary fibrosis (IPF). IPF is a chronic lung condition associated with alterations in glucose metabolism and characterized by fibrosis accumulation in alveolar cells, leading to breathing difficulties.
- - cell culture equipment;
- - molecular biology lab equipment;
- - microscopy facilities, including electron microscopy;
- - sequencing facilities.
- Still in development
Pros, cons & Future potential
- - cellular diversity,
- - functional model,
- - development model,
- - physiological and disease model,
- - regeneration studies,
- - easy to culture,
- - high material availability,
- - easy to genetically modify.
- - absence of human body's microenvironment,
- - lab differences in between protocols,
- - variability from batch-to-batch experiment.
- - lung organoids on a chip,
- - pollution effect on lung development,
- - lung development studies,
- - lung physiology and pathology studies.
References, associated documents and other information
1) Romitti, M. et al. Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism. Nat. Commun. 13, 7057 (2022);
2) Goulburn, A. L. et al. A targeted NKX2.1 human embryonic stem cell reporter line enables identification of human basal forebrain derivatives. Stem Cells Dayt. Ohio 29, 462–473 (2011);
3) Longmire, T. A., Ikonomou, L. & Kotton, D. N. Mouse ESC Differentiation to Nkx2.1+ Lung and Thyroid Progenitors. Bio-Protoc. 2, e295 (2012);
4) Serra, M. et al. Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification. Dev. Camb. Engl. 144, 3879–3893 (2017).
PhD position is funded by the Belgian Kids' Fund (HUDERF)
Contact person
Alessandra BoggianOrganisations
Université Libre de Bruxelles (ULB)IRIBHM-Jacques Dumont
Mirian Romitti Lab
Belgium
Brussels Region