Modeling lung development and pulmonary diseases using human organoids

In the anterior foregut endoderm, Nkx2.1+ progenitor cells give rise to both thyroid follicular cells, which produce thyroid hormones, and lung/airway epithelial cells, including mucus-secreting, ciliated, basal, Clara, and alveolar cells (types 1 and 2). This developmental link explains the Brain-Lung-Thyroid syndrome, observed in patients with NKX2-1 mutations, which affects multiple organ systems.

Despite this known connection, the molecular networks governing the fate decisions of Nkx2.1+ progenitor cells—determining whether they develop into thyroid or lung epithelium—remain largely unexplored.

Our lab has developed a protocol to generate hormone-producing human thyroid organoids from hESCs in vitro. Interestingly, we found that introducing just a single hormone into the culture conditions completely suppresses thyroid differentiation, instead promoting the formation of lung organoids containing both airway and alveolar compartments.

Current Research Goals

Using advanced technologies such as scRNA-seq, ATAC-seq, and CRISPR gene editing, our research aims to:

1. Map the dynamic gene expression patterns underlying human thyroid and lung development in our organoid models.

2. Unravel the molecular networks controlling the lineage decisions of Nkx2.1+ progenitor cells toward thyroid or lung fates.

3. Identify pathways that expand lung progenitor cell populations, with the goal of enhancing lung regeneration and repair studies.

Modeling Human Lung Diseases

Beyond developmental biology, we are leveraging our highly differentiated lung organoids as a powerful tool to model human pulmonary diseases, including:

• Congenital lung disorders

• Idiopathic Pulmonary Fibrosis (IPF)

• Pollution-induced respiratory conditions

• Viral infections

By integrating organoid technology with functional genomics, our research aims to uncover fundamental mechanisms of lung and thyroid development, while also paving the way for innovative approaches to disease modeling and regenerative medicine.