Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals
- Macrina Lobo
- Ellen Johansson
- Sima Kumari
- Elin Schoultz
- Isak Ahlinder
- Shawn Liang
- Therese Carlsson
- Bengt R. Johansson
- Pina Marotta
- Mario De Felice
- Jakob Dahlberg
- Carolina Guibentif
- Henrik Fagman
- René Maehr
- Mikael Nilsson
2026-05-25
The thyroid has a remarkable evolution, transforming from an exocrine constituent of the chordate endostyle to an endocrine gland in basal vertebrates. In mammals, a second endocrine cell type of presumed neural crest origin appears, although recent lineage tracing has firmly established thyroid C-cells are also endoderm-derived. Here, we characterize the global gene expression in both embryonic thyroid lineages at single-cell level and identify lineage-specific transcription factors and their network regulation of target genes implicated in thyroid development into a dual endocrine organ. Merging of the pharyngeal pouch-derived ultimobranchial bodies with the midline thyroid primordium is an ordered process featuring basement membrane dynamics and epithelial-mesenchymal plasticity required for precursor cells to disseminate and properly integrate, thus forming the typical histoarchitecture of thyroid follicles and parafollicular C-cells. Synchronous lineage growth of compound follicles is recapitulated in mixed-type thyroid carcinoma in which only the neuroendocrine tumor cells escape the follicle basement membrane boundaries and become invasive adopting a C-cell precursor-like migratory phenotype.